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Abstracts by Tom Swartz
Intralesional Resection in Treating Patients With Chondrosarcoma of the Bone This Phase II trial is currently recruiting patients. Intralesional resection is a less invasive type of surgery for chondrosarcoma of the bone and may have fewer side effects and improve recovery. The purpose of this trial is to study how well intralesional resection works in treating patients with low-grade chondrosarcoma of the bone. Patients undergo intralesional resection (curettage with high-speed burr). Patients then receive local adjuvant treatment comprising of liquid nitrogen, phenol, alcohol, or argon beam to the excision site. The bone cavity is then filled with either polymethyacrylate cement or a bone graft (allograft or homograft). Patients may also have a metal plate installed at the wound site. Patients are followed every 3 months for 1 year and then every 6 months for 4 years. A total of 60 patients will be accrued for this study within 30-60 months. Patients 18 years of age and older are eligible. This trial is taking place at centers in Arkansas, Colorado, Florida, Michigan, Minnesota, Missouri, New Mexico, Oregon, Utah, and Washington.
This Phase II trial is currently recruiting patients. Pemetrexed disodium (Alimta) is a potent new antifolate which inhibits many folate-dependent reactions that are essential for cell proliferation. Its primary target is thymidylate synthase but it also inhibits folate-dependent enzymes involved in purine synthesis. Cells that are resistant to antifolates are generally less resistant to pemetrexed, irrespective of the mechanism of resistance. Pemetrexed has shown good activity in preclinical models with human tumor cells and xenografts. In the majority of clinical trials of pemetrexed, the dose-limiting toxic effect is neutropenia; other side-effects are mostly gastrointestinal. Preclinical studies indicate that the toxic effects of pemetrexed can be reduced by dietary folate, resulting in an improved therapeutic index. Low folate status is also associated with higher levels of toxicity in patients. As a single agent pemetrexed has shown good activity against non-small-cell lung cancer, squamous-cell carcinoma of head and neck, colon cancer, and breast cancer, and it appears to be particularly active in combination with cisplatin against non-small-cell lung cancer and mesothelioma. The purpose of this trial is to study how well pemetrexed disodium works in treating patients with recurrent and unresectable or metastatic chondrosarcoma. Patients are stratified according to prior chemotherapy (yes vs. no). The treatment outline is as follows. Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses repeat every 21 days* in the absence of disease progression or unacceptable toxicity (NOTE: *The duration of course 1 is 28 days; the duration of all subsequent courses is 21 days). Beginning 7 days before the first dose of pemetrexed disodium and continuing until 21 days after the completion of pemetrexed disodium, patients receive cyanocobalamin (vitamin B-12) intramuscularly once every 63 days and oral folic acid once daily. Patients achieving a complete response (CR) receive 2 additional courses beyond CR. Patients achieving a confirmed partial response (PR) that is resectable, proceed to surgical resection and then receive 2 additional courses of therapy after recovering from surgery. Patients achieving a confirmed PR that is not resectable continue treatment in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 5 years. A total of 40-75 patients (20-40 in the previously treated stratum and 20-35 in the previously untreated stratum) will be accrued for this study within 20-37.5 months. Patients 18 years of age and older are eligible. This trial is taking place at centers in California, Illinois, Kansas, Missouri, Montana, North Carolina, South Carolina, and Wyoming.
Gemcitabine and Docetaxel to Treat Bone and Soft Tissue Cancers This Phase II trial is currently recruiting patients. This study will examine the side effects and possible benefits of the anti-cancer drugs gemcitabine (Gemzar) and docetaxel (Taxere) in patients with bone or soft tissue cancer (sarcoma); determine how the body absorbs and eliminates the drugs; and perform genetic studies on the tumor and try to grow the tumor in the laboratory or in animals. Patients 10 years of age and older with recurrent osteosarcoma, Ewing's sarcoma, and inoperable or recurrent inoperable chondrosarcoma may be eligible for this study. Participants receive gemcitabine and docetaxel in 21-day cycles as follows: Gemcitabine is given as a 90-minute infusion on days 1 and 8 of each cycle. Docetaxel is given as a 60-minute infusion following the gemcitabine infusion on day 8 of each cycle. Filgrastim is given as an injection under the skin either: 1) daily, beginning the day after each docetaxel infusion and continuing until the bone marrow is recovered from chemotherapy (usually 7 to 10 days); or 2) in a long-acting form on the day after the docetaxel infusion. Filgrastim boosts production of blood cells that have been depleted as a result of chemotherapy. Patients are taught to self-administer the injections. Treatment will continue for a total of 14 cycles or until the patient's tumor gets larger, side effects are unacceptable, the patient decides to stop treatment, or further treatment would not be in the patient's best interest. At the end of chemotherapy, patients will be monitored for treatment side effects and disease progress, initially every 3 months and then every 6 months until 2 years from finishing treatment. The total expected enrollment is 20 patients. This trial is taking place at the National Cancer Institute, Bethesda, Maryland.
Drugs used in chemotherapy, such as gemcitabine and docetaxel, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining gemcitabine with docetaxel may kill more tumor cells. The purpose of this trial is to study the effectiveness of combining gemcitabine with docetaxel in treating patients who have recurrent osteosarcoma, recurrent Ewing's sarcoma, or unresectable or locally recurrent chondrosarcoma. Patients are stratified according to diagnosis (recurrent osteosarcoma vs. recurrent Ewing’s sarcoma vs. unresectable or locally recurrent chondrosarcoma). Patients receive gemcitabine IV over 90 minutes on days 1 and 8 and docetaxel IV over 1 hour on day 8. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 9 and continuing until blood counts recover. Patients may receive pegfilgrastim SC on day 9 (once per course) as an alternative to G-CSF. Treatment repeats every 21 days for up to 14 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 1 year and then every 6 months for 1 year. A maximum of 120 patients (40 per stratum) will be accrued for this study within 17-24 months. Patients 4 years of age and older are eligible. This trial is taking place at centers in California, the District of Columbia, Georgia, Illinois, Maryland, Massachusetts, Michigan, Minnesota, New York, and Texas.
This Phase II trial is currently recruiting patients. Imatinib mesylate (Gleevec) may stop the growth of tumor cells by blocking the enzymes necessary for their growth. The purpose of this trial is to study how well imatinib mesylate works in treating patients with locally advanced or metastatic dermatofibrosarcoma protuberans or giant cell fibroblastoma. Patients receive oral imatinib mesylate twice daily for at least 14 weeks in the absence of disease progression or unacceptable toxicity. Patients with stable disease after 14 weeks receive imatinib mesylate for 12 additional weeks. Patients with a partial or complete response at 14 weeks undergo surgical resection if possible. If surgical resection of all remaining tumor is not possible OR if complete resection is not achieved (section margins positive), patients continue to receive imatinib mesylate in the absence of disease progression. Patients are followed monthly for 6 months, every 3 months for 6 months, every 6 months for 2 years, and then annually thereafter. A total of 44 patients will be accrued for this study within 2 years. Patients 18 years of age and older are eligible. This trial is taking place at centers in Belgium and the Netherlands.
This Phase II trial is currently recruiting patients. Imatinib mesylate (Gleevec) may stop the growth of tumor cells by blocking the enzymes necessary for their growth. The purpose of this trial is to study how well imatinib mesylate works in treating patients with locally recurrent or metastatic dermatofibrosarcoma protuberans (DFSP) or transformed fibrosarcomatous DFSP (a type of soft tissue sarcoma). Patients receive oral imatinib mesylate once daily on days 1-56. Treatment repeats every 56 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients with documented tumor progression and no serious side effects may continue therapy at a higher dose for another 6 courses. Patients are followed every 6 months for 2 years and then annually for 3 years. A total of 20-40 patients will be accrued for this study within 10 months-3.4 years. Patients 18 years of age and older are eligible. This trial is taking place at centers in Arkansas, Colorado, Illinois, Indiana, Kansas, Michigan, Minnesota, Missouri, Montana, North Carolina, Ohio, South Carolina, Washington, West Virginia, and Wyoming.
This Phase I trial is currently recruiting patients. The purpose of this study is to learn if a vaccine made from the patient's own tumor cells then genetically modified to secrete GM-CSF will delay or stop the growth of the tumor. It will also look at the vaccine's effects on the immune system and the side effects of giving a vaccine made from a subject's own cancer cells. The trial is open to patients with clear cell sarcoma, alveolar soft part sarcoma, pediatric renal cell carcinoma (25 years of age and younger), and children (18 years of age and younger) with stage IV melanoma. The treatment outline is as follows:
The total expected enrollment is 36 patients. This trial is taking place at the Dana-Farber Cancer Institute and Children's Hospital, Boston, Massachusetts.
Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Sarcoma This Phase II trial is currently recruiting patients. Sorafenib is a "targeted drug" engineered to inhibit something called the RAF kinase within cancer cells. RAF in turn is part of the RAS oncogene pathway. RAS is a gene which drives cell division and is overexpressed in many cancers. In addition to targeting RAF kinase, sorafenib also inhibits the VEGF and PDGF receptors on blood vessel cells. Thus, sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. The purpose of this trial is to study how well sorafenib works in treating patients with metastatic, locally advanced, or recurrent sarcoma. Patients are stratified according to sarcoma histology (angiosarcoma vs. malignant peripheral nerve sheath tumor vs. leiomyosarcoma vs. high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma] vs. fibrosarcoma vs. all other types of sarcoma). Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study, patients are followed at 4 weeks. A total of 222 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at centers in Illinois, Michigan, New York, Ohio, South Carolina, and Texas.
Sorafenib in Treating Patients With Advanced or Recurrent Uterine Cancer This Phase II trial is currently recruiting patients. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor (see the sorafenib trial listed above) The purpose of this trial is to study how well sorafenib works in treating patients with advanced or recurrent uterine cancer, including recurrent uterine sarcoma. Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. A total of 74 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at centers in California, Illinois, Indiana, Michigan, Missouri, Pennsylvania, Wisconsin, and Ontario Canada.
Trastuzumab in Treating Patients With Locally Advanced or Metastatic Synovial Sarcoma This Phase II trial is currently recruiting patients. Trastuzumab is a monoclonal antibody; it may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The purpose of this trial is to study how well trastuzumab works in treating patients with locally advanced or metastatic synovial sarcoma. Patients receive trastuzumab (Herceptin^®) IV over 90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 6 weeks until disease progression and then every 6 months for up to 2 years from study entry. A total of 20-40 patients will be accrued for this study within 10-40 months. Patients 18 years of age and older are eligible. This trial is taking place at centers in Illinois, Indiana, Iowa, Kansas, Missouri, Montana, North Carolina, Ohio, South Carolina, Utah, Washington, and Wyoming.
FR901228 in Treating Patients With Metastatic or Unresectable Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. FR901228 is a type of depsipeptide and belongs to the family of drugs called histone deacetylase inhibitors. Depsipeptide binds to and inhibits histone deacetylase, thereby affecting the regulation of gene expression and inducing cell differentiation, cell cycle arrest, and apoptosis. This agent also inhibits hypoxia-induced angiogenesis and depletes several HSP90-dependent oncoproteins. The purpose of this trial is to study how well FR901228 works in treating patients with metastatic or unresectable soft tissue sarcoma. Patients receive FR901228 IV over 4 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 6 additional courses beyond documentation of CR. After completion of study treatment, patients are followed every 2 months. A total of 18-36 patients will be accrued for this study within approximately 1 year. Patients 18 years of age and older are eligible. This study is taking place at centers in Arizona, California, Georgia, Illinois, Kentucky, North Carolina, Ohio, South Carolina, and Virginia.
Chemo Drug Sensitivity Microculture (MiCK) Assay for Apoptosis This Phase II/III trial is currently recruiting patients. Identification of those patients who will or will not respond to a specific chemotherapy is important for making decisions regarding chemotherapy regimens as well as alternative management approaches. A laboratory test that could help to determine the sensitivity of an individual patient’s tumor cells to specific chemotherapeutic agents would be valuable in choosing the optimal chemotherapy regimen for that patient with an expectation of increasing the response rate to the therapy. Several types of in vitro assays that measure tumor cell survival following exposure to cytotoxic agents have been evaluated for their ability to predict chemotherapy outcomes. As a group, these assays are referred to as drug resistance assays. In a resistance assay, the surviving tumor cells can be detected directly by their exclusion or metabolism of specific dyes. Alternatively, since some of tumor cells are proliferating, their survival can be detected by measurement of DNA synthesis by radiolabeled precursor incorporation or demonstration of clonogenic potential by growth into colonies in semi-solid culture medium. In several clinical studies, these assays were useful in detecting drug resistance and in predicting a poor prognosis for cancer patients. However, these resistance assays cannot detect sensitivity of an individual patient’s tumor cells to a specific drug. Therefore, new methods determining drug-sensitivity of the tumor cells of an individual patient and, thus, capable of both predicting a positive treatment outcome and guiding chemotherapy, would be of significant value. Recently, Dr. Kravtsov has developed an automated microculture kinetic (MiCK) assay for measuring drug induced apoptosis in tumor cells. Apoptosis is a distinct mode of cell death which occurs under physiological conditions and yet can be induced in malignant cells by chemical and physical factors including antitumor drugs. During the last decade, it has been recognized that chemotherapeutic agents exert their antitumor activity by triggering apoptosis in susceptible tumor cells. This implies that the MiCK assay for apoptosis provides a mechanism-based approach to studying effects of cytotoxic agents on tumor cells. Unlike “resistance” assays that measure a fraction of cells surviving drug exposure, the MiCK assay measures a fraction of tumor cells killed by a chemotherapeutic agent via mechanism of apoptosis. Therefore the MiCK assay determines drug sensitivity, rather than resistance. Recently the MiCK assay has been shown to predict complete remission rate and survival in acute myeloid leukemia patients better than clinical criteria did. In a limited study, the MiCK assay has been used to direct chemotherapy of the leukemia patients. The MiCK assay has also been used to study drug-induced apoptosis in solid tumors, including neuroblastoma and colon adenocarcinoma cell lines. More recent data has demonstrated that the MiCK assay can detect drug induced apoptosis in primary cultures of tumor cells isolated from patients with ovarian carcinoma, gastric carcinoma, metastatic breast cancer and high grade soft tissue sarcoma. DiaTech is a private company performing patient specific cancer chemosensitivity testing for patients and physicians. DiaTech Oncology is doing this clinical study to see if this new experimental MiCK technology assay will predict treatment outcome and can help to direct chemotherapy of cancer subjects, including those with soft tissue sarcoma. Patients must have tumor which is accessible and agree to undergo biopsies. The more viable tumor tissue is submitted for the study, the more chemotherapeutic agents can be tested against the tumor cells. Drug selection for testing against tumor cells will be based on the previous chemotherapy history of an individual patient with consideration of the future treatment plans. The drugs will be selected from a compendium of agents recommended for the treatment of the patient’s malignancy. Patients 18 to 85 years of age are eligible. The total expected enrollment is 150 patients. This trial is taking place at centers in Tennessee and Texas.
This Phase I trial is currently recruiting patients. Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances, such as radioactive iodine, to them without harming normal cells. The purpose of this trial is to study the side effects and best dose of radiolabeled monoclonal antibody therapy in treating patients with refractory, recurrent, or advanced CNS or leptomeningeal cancer, including patients with Ewing's sarcoma/primitive neuroectodermal tumor, rhabdoid tumor, osteosarcoma, desmoplastic small rounded-cell tumor, and rhabdomyosarcoma. This is a dose-escalation study. Patients receive iodine I 131 monoclonal antibody 8H9 (^131I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of ^131I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 3-30 patients will be accrued for this study within 2-3 years (study began approximately August 2004). Patients of all ages are eligible. This study is taking place at Memorial Sloan-Kettering Cancer Center, New York,
Combination Therapy of Interleukin-12 and Interleukin-2 to Treat Advanced Cancer This Phase I trial is currently recruiting patients. Interleukin-2 is an approved drug for treating melanoma and kidney cancer. Interleukin-12 is an experimental drug that has shown anti-cancer activity in animals, shrinking tumors and slowing their growth. Animal studies suggest that given together, the drugs may be more effective against cancer than either one singly. The purposes of this study are fourfold. It will 1) determine what dose of interleukin-12 (IL-12) and interleukin-2 (IL-2) combination therapy can be given safely to patients with advanced cancer; 2) evaluate the side effects of this treatment; 3) examine how the body handles this drug combination; and 4) determine whether and how the therapy may cause the immune system to stop or slow tumor growth. Patients 18 years of age and older with advanced solid-tumor cancers, including sarcomas, that do not improve with standard treatment may qualify for this study. Candidates will have a physical examination, including blood and urine tests, electrocardiogram (EKG) and echocardiogram, DTH skin test (to test the function of the immune system), chest X-ray and lung function tests to determine eligibility. Bone marrow biopsy and imaging procedures such as CT and MRI scans may also be required. Patients over 50 years old will also undergo exercise stress testing.
Treatment will consist of four courses of IL-2 and IL-12. On days one and nine of each course, patients will receive three doses (one every 8 hours) of IL-2 intravenously. On days two, four, six, 10, 12 and 14, they will receive IL-12 intravenously. This will be followed by a recovery period from days 15 through 35. This regimen will be repeated for another three cycles; patients who show benefit without severe side effects may continue for additional cycles. Treatment for the first cycle will be administered in the hospital. If the drugs are well tolerated, additional therapy may be given on an outpatient basis.
A biopsy will be done at the beginning of the study, after completing the first treatment cycle, and possibly again when the cancer slows, stops or gets worse, or if the patient leaves the study. These tumor samples will be examined to evaluate the effects of treatment. Several blood samples also will be collected during the course of treatment to monitor immune system effects. A device called a heparin lock may be put in place to avoid multiple needle sticks. The total expected enrollment is 44 patients. This trial is taking place at the National Cancer Institute, Bethesda, Maryland.
Stem Cell Transplantation for Metastatic Solid Tumors This Phase II trial is currently recruiting patients. The goal of this study is to identify types of cancer that may be treatable with stem cell transplantation. Patients with a variety of different types of cancerous tumors, including sarcoma, that have metastasized and whose conditions have not improved with stand therapy, will be eligible to participate. Patients selected to participate in the study will undergo a procedure known as a "mini-transplant". The mini-transplant is a transplantation of stem-cells collected from a sibling (brother or sister) of the patient. Unlike traditional bone marrow transplants, the mini-transplant does not require intense chemotherapy or radiation therapy. Because of this, patients experience fewer and less severe side effects. The total expected enrollment is 150 patients. Patients 10 to 80 years of age are eligible. This study is taking place at the National Heart, Lung and Blood Institute, Bethesda, Maryland.
A Study of Anti-CTLA4 Antibody in People with Advanced Synovial Sarcoma This Phase II is currently recruiting patients. The investigators of this study will try to exploit some of the proteins made by synovial sarcoma (cancer-germ cell or cancer-testis antigens) as targets for the immune system. Specifically, they will investigate if immune-based therapy with anti-CTLA4 antibody once every 4 weeks for three treatments will activate the immune system enough to attack recurrent synovial sarcoma. In this study the tumor itself will serve as the "vaccine" or source of protein to activate tumor-fighting T cells with the anti-CTLA4. Anti-CTLA4 takes the brakes off the immune system to allow otherwise hidden immune responses to become more active. In so doing, there could be other side effects, such as immune system attacks against the normal organs of the body. Thus, the investigators will follow both the anti-tumor immune responses with frequent blood tests and follow and treat side effects people develop on this study to determine if anti-CTLA4 is worth pursuing in a larger number of patients with synovial sarcoma or other sarcomas. Patients 18 years of age and older are eligible. The total expected enrollment is 17 patients. The trial started July 2005 and it is expected to be completed in March 2007. This study is taking place at Memorial Sloan-Kettering Cancer Center, New York.
This Phase II trial is currently recruiting patients. The purpose of this trial is to study how well paclitaxel works in treating patients with locally advanced or metastatic soft tissue angiosarcoma or lymphangiosarcoma that cannot be removed by surgery. Patients receive paclitaxel IV on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses. A total of 15-30 patients will be accrued for this study. Patients 18 to 70 years of age are eligible. This trial is taking place at several centers in France.
This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs. without ifosfamide and pegfilgrastim as first-line therapy. Patients are stratified according to WHO performance status (0 vs. 1), age group (less than 50 years of age vs. 50 years of age and over), presence of liver metastases (yes vs. no), histological grade (2 vs. 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. The following sarcomas are eligible: malignant fibrous histiocytoma, myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, synovial sarcoma, myxofibrosarcoma (intermediate and high-grade), fibrosarcoma, leiomyosarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, epithelioid sarcoma, alveolar rhabdomyosarcoma, unclassifiable sarcoma, not otherwise specified. A total of 450 patients will be accrued for this study within 4 years (study start 5/2003). Patients 18 to 60 years of age are eligible. This trial is taking place at centers in Austria, Belgium, Denmark, France, Germany, the Netherlands, Slovakia, Spain, and the United Kingdom.
Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma This phase I/II trial is not yet open for patient recruitment. Nelfinavir mesylate is a protease inhibitor which may help prevent cancer cells from spreading. The purpose of this trial is to study the side effects and best dose of nelfinavir mesylate and to see how well it works in treating patients with recurrent, metastatic, or unresectable liposarcoma. This is a phase I dose-escalation study followed by a phase II study. In the Phase I part of the study, patients receive oral nelfinavir mesylate twice daily in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of nelfinavir mesylate until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. In the Phase II part of the study, patients receive nelfinavir mesylate as in phase I at the MTD. A total of 40 patients will be accrued for this study. Patients 18 years of age and older are eligible. The location of this trial has not been identified.
This Phase II trial is currently recruiting patients. The purpose of this study is to provide access to treatment with trabectedin before the drug is commercially available and reimbursable to patients who previously received treatment for soft tissue sarcoma, who have relapsed or who are refractory to/intolerant of standard therapies. Trabectedin (ET-743, Yondelis) is the first of a new class of antitumor agents. Previous studies with trabectedin in patients who had been previously treated for soft tissue sarcoma have suggested that treatment with trabectedin resulted in tumor shrinkage, disease stabilization, and improved survival rates. However, hematologic toxicity, hepatic toxicity, and renal impairment were also observed in these patients. This is a single-arm, open-label, multicenter, study that is designed to provide access to trabectedin in patients with soft tissue sarcoma who are not expected to benefit from currently available therapeutic options for the treatment of soft tissue sarcoma. The safety profile of trabectedin will be evaluated to further assess the potential risks of trabectedin treatment in patients previously treated for soft tissue sarcoma. Safety evaluation will include physical examinations, monitoring of vital signs and adverse events, and assessing clinical laboratory tests and 12-lead electrocardiogram results. Eastern Cooperative Oncology Group (scale used by researchers to represent the level of activity a patient is capable of) performance status will also be assessed. The treatment outline is as follows: 1.5 mg/m2 trabectedin reconstituted and diluted to 500 mL volume will be administered by central venous line over 24 hours at start of each 21-day treatment cycle; 20 mg dexamethasone, an anti-inflammatory agent, will be administered by vein 30 minutes before each trabectedin dose. The number of cycles will be response dependent. The total expected enrollment for this trial is 200 patients. Patients 18 years of age and older are eligible. This trial is taking place at centers in California, Idaho, Illinois, Massachusetts, Michigan, Minnesota, New Jersey, New York, Oregon, South Carolina, and Canada.
This phase II trial is currently recruiting patients. The purpose of this study is to determine the antitumor activity of vinorelbine + cyclofosfamide in patients with a refractory tumor or in relapse in rhabdomyosarcomas and other soft part tissue tumors, Ewing’s tumors, osteosarcomas, neuroblastomas or medulloblastomas. The total expected enrollment is 210 patients (the study started in June 2003). Patients 12 months to 25 years of age are eligible. This study is taking place at the Institut Gustave-Roussy, Villejuif, France.
Combination Chemotherapy, PEG-Interferon Alfa-2b, and Surgery in Treating Patients With Osteosarcoma This Phase III trial is currently recruiting patients. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Biological therapies, such as PEG-interferon alfa-2b, may interfere with the growth of tumor cells. Giving combination chemotherapy before surgery may shrink the tumor so it can be removed. Giving combination chemotherapy together with PEG-interferon alfa-2b after surgery may kill any remaining tumor cells. It is not yet known whether giving combination therapy together with PEG-interferon alfa-2b is more effective than two different combination chemotherapy regimens alone after surgery in treating osteosarcoma. Thus, the purpose of this trial is to study combination chemotherapy followed by surgery and two different combination chemotherapy regimens with or without PEG-interferon alfa-2b to compare how well they work in treating patients with osteosarcoma. The treatment outline is as follows:
In both groups, treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 1½-3 months for 2 years, every 2-4 months for 2 years, every 6 months for 6 years, and then every 6-12 months thereafter. A total of 1,400 patients (630 good responders and 770 poor responders) will be accrued for this study within 4 years. Patients between 5 and 40 years of age are eligible. Patients who have received prior treatment for osteosarcoma are not eligible. This trial is taking place at centers in Canada, Germany, Norway, and the United Kingdom.
This Phase II/III trial is currently recruiting patients. In 1986, St. Jude Children’s Research Hospital researchers initiated a trial (OS86) of ifosfamide, cisplatin, doxorubicin, and high-dose methotrexate. A subsequent trial (OS91), which was completed in 1997, substituted carboplatin for cisplatin. The 5-year survival estimates for patients with localized osteosarcoma were 69.2%±7.4% for those treated on OS86 and 73.1%±7.0% for those treated on OS91 (P=0.84). The results of OS91 demonstrated that the carboplatin and ifosfamide combination has substantial antitumor activity. When used with doxorubicin and high-dose methotrexate to treat localized osteosarcoma, this combination yielded outcomes comparable to those of trials using cisplatin-based therapy, with less long-term toxicity. On the basis of these results and the results of other studies that have eliminated high-dose methotrexate, St. Jude Children’s Research Hospital researchers are conducting this current trial to evaluate ifosfamide, carboplatin, and doxorubicin as an up-front therapy before surgery for localized and resectable osteosarcoma. The investigators believe that high-dose methotrexate may interfere with the dose-intensive delivery of the other agents, and thus, has been eliminated from this study. A total of 70 patients will be recruited for this study. Patients who have received prior chemotherapy are not eligible. Patients 25 years of age and younger are eligible. This trial is taking place at St. Jude Children's Research Hospital, Memphis, Tennessee.
This Phase II trial is currently recruiting patients. Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane are widely used drugs in the treatment of sarcomas. ImmTher is an investigational agent which stimulates the body's white blood cells to attack and kill tumor cells. The goal of this study is to see if treatment with vincristine, doxorubicin, cyclophosphamide and dexrazoxane (VACdxr) given in high doses with or without ImmTher will help patients with Ewing's sarcoma live longer. The safety of these treatments will also be studied. The total expected enrollment is 104 patients. Patients between 3 and 60 years of age are eligible. This trial is taking place at University of Texas M.D. Anderson Cancer Center, Houston, Texas.
This phase II trial is currently recruiting patients. It is open to patients that have histologically proven leiomyosarcoma of the uterus or other sites considered unresectable for cure. No previous chemotherapy is allowed, but patients may have received prior radiation provided it is completed >6 weeks prior to inclusion. It is a study of gemcitabine and docetaxel as a first line treatment. A total of 44 patients will be recruited. The trial is taking place in the United Kingdom. For further details, contact Jennifer Morrison (jennifer.morrison@rmh.nthames.nhs.uk).
This Phase III trial is currently recruiting patients. The purpose of this trial is to compare the progression-free and overall survival of patients with locally advanced or metastatic soft tissue sarcoma treated with doxorubicin with vs. without ifosfamide and pegfilgrastim as first-line therapy. Patients are stratified according to WHO performance status (0 vs. 1), age group (less than 50 years of age vs. 50 years of age and over), presence of liver metastases (yes vs. no), histological grade (2 vs. 3), and participating center. Patients are randomized to 1 of 2 treatment arms as follows:
In both arms, treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 8 weeks until disease progression and then every 12 weeks thereafter. The following sarcomas are eligible: malignant fibrous histiocytoma, myxoid and round cell liposarcoma, pleomorphic liposarcoma, or dedifferentiated liposarcoma, pleomorphic rhabdomyosarcoma, synovial sarcoma, myxofibrosarcoma (intermediate and high-grade), fibrosarcoma, leiomyosarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, epithelioid sarcoma, alveolar rhabdomyosarcoma, unclassifiable sarcoma, not otherwise specified. A total of 450 patients will be accrued for this study within 4 years (study start 5/2003). Patients 18 to 60 years of age are eligible. This trial is taking place at centers in Austria, Belgium, Denmark, France, Germany, the Netherlands, Slovakia, Spain, and the United Kingdom.
Bendamustin Hydrochloride in Patients with Soft Tissue Sarcoma This Phase II trial is currently recruiting patients. Bendamustin is a bifunctional alkylating agent with low toxicity that produces both single and double strand breaks of DNA. It has show anti-tumor activity against Hodgkin’s and non-Hodgkin’s lymphomas, multiple myeloma, and chronic lymphatic leukemia. The aims of this trial are to evaluate the efficacy of bendamustin in patients with metastatic soft tissue sarcoma who have progressed after or during an anthracycline-based chemotherapy and to assess its toxicity. Patients 18 years of age and older are eligible. This trial is taking place at Medical center II, University of Tuebingen, Tuebingen, Germany.
This Phase I study is currently recruiting patients. The purpose of this clinical trial is to study the effectiveness of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) in treating young patients who have recurrent or refractory leukemia or selected solid tumors, including rhabdomyosarcoma, Ewing’s sarcoma, and osteosarcoma. Patients receive 17-AAG IV over 1 hour on days 1, 4, 8, and 11 (for patients with solid tumors) OR days 1, 4, 8, 11, 14, and 18 (for patients with leukemia). Courses for all patients repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 15 patients are treated at the MTD. Patients are followed for 30 days. A total of 70 patients (35 per stratum) will be accrued for this study within 23.3-35 months. Patients up to 21 years of age eligible. This study is being conducted at cancer centers in Arizona, Colorado, Florida, Georgia, Maryland, New York, Tennessee, and Texas.
This Phase II trial is currently recruiting patients. The purpose of this study is to explore how sarcomas are affected by a new medication, cetuximab. Cetuximab is directed towards a protein called EGFR (epidermal growth factor receptor), that is found in some types of cancer. Studies have shown that this drug can be beneficial in patients with colon cancer and has been approved by the US Food and Drug Administration (FDA) for this purpose. The investigators are conducting this study to see if it is beneficial in patients with sarcoma. Patients with unresectabale or metastatic high grade soft tissue or bony sarcoma 16 years of age and older are eligible. This trial is taking place at the University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan.
This Phase I trial is currently recruiting patients. This phase I trial is studying the side effects and best dose of giving 17-AAG together with bortezomib in treating patients with advanced solid tumors or lymphomas. This is a dose-escalation study. Patients receive 17-AAG IV over 1 hour and bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, at least 12 additional patients (6 patients with solid tumors and 6 patients with lymphoma) are treated as above* at the MTD. NOTE: *Bortezomib is not administered on day 1 of course 1 only. Patients are followed at 3 months. A total of 3-42 patients (3-36 with solid tumors and 6 with lymphoma) will be accrued for this study within 10.3 months-3.5 years. Patients 18 years of age and older are eligible. This trial is taking place at the Warren Grant Magnuson Clinical Center, Bethesda, Maryland and the Mayo Clinic Cancer Center, Rochester, Minnesota.
This Phase I trial is currently recruiting patients. This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when given together with paclitaxel in treating patients with metastatic or unresectable solid tumor. This is a dose-escalation study of 17-AAG. Patients receive 17-AAG IV over 1 hour on days 1*, 4, 8, 11, 15 and 18 and paclitaxel IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: *17-AAG is not administered on day 1 of course 1. Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6-12 patients are treated at the recommended phase II dose. A total of 6-35 patients will be accrued for this study within 2-11.7 months. Patients 18 years of age and older are eligible. This trial is taking place at the Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio and the Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
Combination Chemotherapy in Treating Patients With Advanced Solid Tumors This Phase I trial is currently recruiting patients. This phase I trial is studying the side effects, best way to give, and the best dose of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) when given together with gemcitabine and/or cisplatin in treating patients with advanced solid tumors. This is a dose-escalation, cohort study of 17-AAG. Patients are assigned to 1 of 3 treatment cohorts as follows: (Note: Cohort A closed to accrual as of 3/2/04; Cohort B closed to accrual as of 3/2/05).
NOTE: ** Gemcitabine and cisplatin dosage is constant, while 17-AAG is escalated in cohorts B, C, and D. NOTE: *** Gemcitabine dosage is constant, 17-AAG is started at a higher dose level than all other cohorts, and cisplatin dosage is escalated in cohort E. Cohorts of 3-6 patients receive escalating doses of 17-AAG until the MTD is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. In all cohorts, courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for 3 months. A total of 12 patients have been accrued for part I (cohort A closed to accrual as of 3/2/04) of this study. An additional 33-66 patients will be accrued for part II (cohorts B [closed to accrual as of 3/2/05], C, D, and E) of this study within approximately 3 years. Patients 18 years of age and older are eligible. This trial is taking place at the Mayo Clinic Cancer Center, Rochester, Minnesota.
Combination Chemotherapy in Treating Patients With Metastatic or Unresectable Solid Tumors This Phase I trial is currently recruiting patients. The purpose of this trial is to study the side effects and best dose of combination chemotherapy 17-AAG and docetaxel in treating patients with metastatic or unresectable solid tumors. This is a dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG). This is a dose-escalation study of 17-AAG. Patients are assigned to 1 of 2 treatment groups as follows:
Cohorts of 3-6 patients per group receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Up to 20 additional patients (10 per group) are treated at the MTD. Approximately 33-96 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at Memorial Sloan-Kettering Cancer Center, New York and the Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
ZD1839 and Oral Irinotecan in Treating Young Patients with Refractory Solid Tumors This Phase I trial is currently recruiting patients. The purpose of this trial is to find the largest dose of the drug irinotecan, in combination with ZD1839, that can be given safely to children and to learn the good and bad effects. Studies performed in the laboratory have shown that ZD1839 helps make available the orally administered irinotecan. In this study the intravenous formula of irinotecan will be given orally on days 1-5 and days 8-12. The dose of ZD1839 will be a fixed dose and will be administered orally on days 1-12. Each course of treatment will consist of 21 days. The administration of irinotecan on day 12 of course 1 and day 2 of course 2 will be an intravenous administration. All other doses and subsequent courses will consist of an orally administered dose. The total expected enrollment is 30 patients. Patients up to 21 years of age are eligible. This trial is taking place at St. Jude Children's Research Hospital, Memphis, Tennessee.
UCN-01 and Irinotecan in Treating Patients With Metastatic or Unresectable Solid Tumors This Phase I trial is currently recruiting patients. Giving UCN-01 together with irinotecan may help kill more cancer cells by making tumor cells more sensitive to the drug. The purpose of this trial is to study side effects and best dose of giving UCN-01 together with irinotecan in treating patients with metastatic or unresectable solid tumors. This is a dose-escalation study. Patients receive irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and UCN-01 IV over 3 hours on days 2 and 23. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of irinotecan and UCN-01 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. A total of 18-21 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at the Siteman Cancer Center at Barnes-Jewish Hospital, Saint Louis, Missouri.
Study of Oral AP23573 to Treat Patients with Refractory or Advanced Malignancies This Phase I trial is currently recruiting patients. AP23573, being developed by Ariad Pharmaceuticals, Inc., is a mTOR inhibitor that starves cancer cells and shrinks tumors by regulating the response of tumor cells to nutrients and growth factors and by controlling tumor blood supply and angiogenesis through effects on vascular endothelial growth factor (VEGF) in tumor and endothelial cells. AP23573 is currently being studied in phase I and phase II clinical trials in patients with advanced cancers. Thus far, these trials have demonstrated that AP23573 has a favorable safety profile and possesses anticancer activity when administered as a 30-minute intravenous (IV) infusion daily x 5 every-two-weeks or on a weekly schedule. The primary objective of this current phase I trial, however, is to study the safety and tolerability of an orally administered dosage form of AP23573. This will be accomplished by an ascending dose study of 3 dosage regimens in patients with unresectable or metastatic cancer that is refractory to standard therapies. Patients 18 years of age and older are eligible. The expected total enrollment is 144 patients. This trial is taking place at the Cancer Therapy Research Center, San Antonio, Texas, and eventually at the Cancer Institute of New Jersey, New Brunswick, New Jersey.
Vaccine Therapy in Treating Patients With Metastatic Solid Tumors This Phase I trial is currently recruiting patients. Vaccines may make the body build an immune response to kill tumor cells. Infusing the vaccine directly into a tumor may cause a stronger immune response and kill more tumor cells. It is not yet known which vaccine may be more effective in treating metastatic solid tumors. The purpose of this trial is to compare the effectiveness of two different vaccines given directly into the tumor in treating patients who have metastatic solid tumors. This is a randomized study with a dose-escalation component. Patients are stratified according to tumor location (cutaneous, subcutaneous, or lymph node metastases vs. visceral metastases). Patients are randomized to 1 of 2 treatment arms as follows:
Treatment in both arms repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional courses. Three patients from the cutaneous disease (CD) stratum are treated at low-dose in each treatment arm. If no more than 1 of 6 patients experience dose-limiting toxicity (DLT), then 6 additional CD patients are randomized to use the high-dose treatment. If no more than 1 of these 6 patients experience DLT, then 12 patients from the visceral disease (VD) stratum are randomized to low-dose treatment. If no more than 2 of 12 VD patients experience DLT, then the next cohort of 12 VD patients is randomized to high-dose treatment. If 3 of the original 12 VD patients experience DLT, then 6 additional VD patients receive low-dose treatment. If no more than 3 of 18 patients experience DLT, then 12 VD patients receive high-dose treatment. Quality of life is assessed at baseline, monthly during therapy, and then at the end of therapy. Patients are followed every 3 months. A total of 42 patients (21 per treatment arm; 12 in the cutaneous stratum and 30 in the visceral stratum) will be accrued for this study within 1-2 years. Patients 18 years of age and older are eligible. Herbert Irving Comprehensive Cancer Center at Columbia University, New York.
Allogeneic Tumor Cell Vaccination in Patients With Solid Tumors This Phase I/II trial is currently recruiting patients. The goal of this study is to apply allogeneic tumor cell vaccination for immunotherapy in patients with micro-metastatic disease and/or in patients at high risk disease progression. The present study will use allogeneic tumor cell lines for tumor cell vaccines that share MHC determinants with the patient aiming to overcome possible restriction of antigen presentation. Patients 18 years of age and older with metastatic solid tumors are eligible. The total expected enrollment is 100 patients. This trial is taking place at the Hadassah Medical Organization, Jerusalem, Israel.
V3N1 ESUN Copyright © 2006 Liddy Shriver Sarcoma Initiative.
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