Clinical Trial News

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Tom Swartz

Inhaled Sargramostim in Treating Patients With First Pulmonary (Lung) Recurrence of Osteosarcoma

This Phase II study is currently recruiting patients.  The investigators of this study believe that inhaling aerosolized sargramostim before surgery may interfere with the growth of osteosarcoma tumor cells that have spread to the lung.  Sargramostim may then kill any tumor cells remaining after surgery. Thus, the purpose of this trial is to study the effectiveness of inhaled sargramostim in treating patients who are undergoing surgery for the first recurrence of osteosarcoma that has spread to the lung.  Patients are assigned to 1 of 2 groups according to the extent of pulmonary recurrence (unilateral or bilateral).  The treatment outline is as follows:

	Initial inhalation therapy: Patients receive inhaled sargramostim (GM-CSF) twice daily on days 1-7. Treatment repeats every 14 days for 2 courses.
	Thoracotomy: Patients undergo thoracotomy on day 22.
	Post-thoracotomy inhalation therapy: Beginning on day 29, patients resume inhalation therapy as above for up to 12 additional courses.
	Unilateral thoracotomy: Patients undergo unilateral thoracotomy on day 1.
	Initial inhalation therapy: Patients receive inhaled GM-CSF twice daily on days 7-14. Treatment repeats every 14 days for 2 courses.
	Contralateral thoracotomy: Patients undergo contralateral thoracotomy on day 29.
	Post-thoracotomy inhalation therapy: Beginning on day 36, patients resume inhalation therapy as above for up to 12 additional courses. Treatment in both groups continues in the absence of disease progression or unacceptable toxicity.

A total of 40 patients will be accrued for this study within 1.6-2 years.  Patients up to 39 years of age are eligible.  This is a large multi-center study taking place in many states as well as in Austria, Canada, Netherlands, New Zealand, and Switzerland.

Neoadjuvant and Adjuvant Pamidronate With Induction and Maintenance Chemotherapy in Treating Patients With Osteosarcoma

This Phase II study is currently recruiting patients.  The drug pamidronate is a bone metabolism regulator which is used in malignancy related hypercalcemia (elevated calcium levels).  The investigators of this study believe that combining pamidronate with chemotherapy may prevent bone metastases and reduce the chance of bone replacement problems by strengthening bones in patients who are undergoing surgery for osteosarcoma.  Thus, the purpose of this trial is to study the effectiveness of combining neoadjuvant and adjuvant pamidronate with induction and maintenance chemotherapy in treating patients who have newly diagnosed osteosarcoma.  Patients are stratified according to extent of disease (localized vs. metastatic).  The treatment outline is as follows:

	Induction therapy: Patients receive standard chemotherapy comprising cisplatin IV over 4 hours and doxorubicin IV over 15-30 minutes on weeks 0 and 5 and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, and 9. Patients also receive pamidronate IV over 2-4 hours beginning approximately 3 days after initiation of chemotherapy on week 0 and repeating once every 4 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
	Surgery*: Patients undergo surgical resection of primary tumor on week 10 and then proceed to maintenance therapy. Patients with metastatic disease undergo further surgery of metastatic sites after recovery from definitive resection of the primary tumor before proceeding to maintenance therapy. NOTE: *Patients who have undergone definitive surgical resection before study entry may proceed to maintenance therapy or, if appropriate, surgical resection of metastatic disease
	Maintenance therapy: Patients receive standard chemotherapy comprising cisplatin IV over 4 hours on weeks 0 and 5; doxorubicin IV over 15-30 minutes on weeks 0, 5, 10, and 15; and high-dose methotrexate IV over 4 hours on weeks 3, 4, 8, 9, 13, 14, 18, and 19. Patients also receive pamidronate as in induction therapy for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for 1 year.

A total of 75 patients (50 with localized disease; 25 with metastatic disease) will be accrued for this study within 3-4 years.  There is no age limitation.  This study is being conducted at Memorial Sloan-Kettering Cancer Center, New York, NY.

Chemotherapy With or Without Trastuzumab in Treating Patients With Metastatic Osteosarcoma

This Phase II study is currently recruiting patients.  Monoclonal antibodies such as trastuzumab can locate tumor cells and kill them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.  Thus, the purpose of this trial is to study the effectiveness of chemotherapy with or without trastuzumab in treating patients who have metastatic osteosarcoma.  Patients are stratified according to tumor HER2 status (positive vs. negative).  The treatment outline is as follows:

	Patients receive induction therapy comprising doxorubicin IV over 20 minutes followed by cisplatin IV over 4 hours on days 1 and 2 of weeks 1 and 6, and methotrexate IV over 4 hours on day 1 of weeks 4, 5, 9, and 10. Patients also receive leucovorin calcium IV or orally every 6 hours beginning 24 hours after each methotrexate dose and continuing for at least 10 doses until methotrexate levels sufficiently decrease. Within 24-36 hours after completion of induction therapy, patients receive filgrastim (G-CSF) daily until blood counts recover.
	Patients undergo resection of any remaining primary tumor and/or metastatic lesions during week 11. Patient who are unable to undergo resection receive radiotherapy between weeks 11 and 17.
	Patients receive post-induction therapy comprising doxorubicin IV over 20 minutes on days 1 and 2 of weeks 17, 25, and 29; cisplatin IV over 4 hours on days 1 and 2 of weeks 17 and 25; methotrexate IV over 4 hours on day 1 of weeks 16, 20, 24, 28, 32, and 33; etoposide IV over 1 hour on days 1-5 of weeks 13, 21, and 34; and ifosfamide IV over 4 hours on days 1-5 of weeks 13, 21, 29, and 34. Patients also receive leucovorin calcium and G-CSF as in induction therapy.
	Patients whose tumors are found to over express HER2 (2+ level of expression) also receive trastuzumab IV over 30-90 minutes once a week for a total of 34 weeks in addition to the chemotherapy regimen.
	Patients are followed monthly for 1 year, every 2 months for 1 year, every 6 months for 2 years, and then annually thereafter.  A total of 80 patients (40 patients per stratum) will be accrued for this study within 2.5 years.  Patients up to 30 years of age are eligible.

This is a large multi-center study taking place in many states as well as in Austria, Canada, Netherlands, New Zealand, and Switzerland.

Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia, Osteosarcoma, or Non-Hodgkin's Lymphoma

This Phase II study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy consisting of trimetrexate glucuronate plus leucovorin in treating children who have recurrent acute lymphoblastic leukemia, recurrent osteosarcoma, or refractory non-Hodgkin's lymphoma.  Patients are stratified according to disease (acute lymphocytic leukemia, non-Hodgkin's lymphoma vs. osteogenic sarcoma).  Patients receive trimetrexate glucuronate orally or IV every 12 hours on days 1-21 and oral leucovorin calcium every 12 hours on days 1-24. Treatment repeats every 4 weeks. Patients with stable or responsive disease may receive up to 4 courses of therapy.  A total of 25 patients will be accrued for this study within 2 years.  Patients up to 21 years of age are eligible.  This study is being conducted at Memorial Sloan-Kettering Cancer Center, New York, NY.

Gemcitabine and Docetaxel to Treat Bone and Soft Tissue Cancers

This Phase II study is currently recruiting patients.  Gemcitabine and docetaxel are active antineoplastic agents with a broad spectrum of clinical activity. In single agent phase I trials, gemcitabine and docetaxel have shown some activity in patients with osteosarcoma.  A variety of schedules and doses of gemcitabine in combination with docetaxel have been studied in clinical trials. Recently, two clinical trials have reported response rates of approximately 50% when the drugs are given sequentially with gemcitabine followed by docetaxel. Most recently, in vitro data supports the synergy of sequential gemcitabine-docetaxel therapy. Thus, the primary objective of this study is to determine the objective response rate of sequential gemcitabine-docetaxel in patients with recurrent osteosarcoma and other sarcomas.  Additionally, the pharmacokinetics of gemcitabine and docetaxel will be studied and when available, tumor samples for cDNA microarray analysis of gene expression and development of cell lines and xenotransplantation models will be obtained.  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 through a catheter (thin plastic tube) placed in an arm vein.
	·   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.

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.  The expected total enrollment is 20 patients.  Patients 10 years of age and older are eligible.  This study is being conducted at the National Cancer Institute (NCI), Bethesda, Maryland.

Bone Cancer: Treatment Outcome Based on Tumor Response  

This Phase II study is currently recruiting patients.  Standard treatment for patients with non-metastatic bone cancer includes chemotherapy, then surgery to remove the tumor, followed by additional courses of chemotherapy. Sixty to 70 percent of patients do well with this treatment. However, some of the drugs are highly toxic, causing serious side effects, and still, 30 to 40% of patients' tumors do not respond.  In this study, patients will be separated into two different courses of treatment to try to: 1) reduce treatment time, number of medicines, and adverse side effects in patients whose tumors are largely destroyed by the first round of chemotherapy, and 2) improve survival in patients whose tumors do respond well to standard treatment.  All patients will receive three doses of the drugs doxorubicin and cisplatin three weeks apart before surgery. Patients whose disease is confined to the bone and whose tumor responds well to the first round of chemotherapy (more than 90% destroyed) will be given another three courses of the same drugs after the tumor is removed.  Other patients will be given three courses of the drugs melphalan and cyclophosphamide after surgery. These are patients whose tumor: is confined to the bone but did not respond well to the chemotherapy administered before surgery; had spread beyond the bone at the time of diagnosis; and could not be removed surgically.  The expected total enrollment is 24 patients.  Patients 25 years of age and under are eligible.  This study is being conducted at the National Cancer Institute (NCI), Bethesda, Maryland.

Alanosine in Treating Patients With Cancer

This Phase II study is currently recruiting patients.  Cells use two principal pathways to produce adenosine, the building block of ATP, a key source of cellular energy.  In cell culture and animal tumor models, alanosine (also known as SDX-102) has been shown to be a potent and selective anti-cancer agent in cancers that have only one of the two pathways to produce adenosine.  Thus, the purpose of this trial is to study the effectiveness of alanosine in treating patients who have soft tissue sarcoma, sarcoma of the bone, including osteosarcoma, mesothelioma, non-small cell lung cancer, or pancreatic cancer.  Patients receive alanosine IV continuously on days 1-5. Treatment repeats every 21 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.  Patients are followed at 28 days.  A total of 50-145 patients (10-29 per tumor type) will be accrued for this study.  Patients 13 years of age and older are eligible.  This study is being conducted at cancer centers in Alabama, Arizona, California, Florida, Illinois, New York, Tennessee, and Texas.

Genetic Study of Children With Soft Tissue Sarcoma or Rhabdomyosarcoma

This diagnostic study is currently recruiting patients. The purpose of this study is to perform genetic testing on children with soft tissue sarcomas including osteosarcoma to identify children who are at risk of developing leukemia from the chemotherapy used to treat sarcoma.  Blood is collected from patients at diagnosis (preferably before chemotherapy or transfusion), at end of therapy, and at 6 months, 1 year, 2 years, and 3 years after therapy.  Patients do not receive the results of the genetic testing and the results do not influence the type or duration of treatment.  A total of 321 patients will be accrued for this study.  Patients up to 17 years of age are eligible.  This is a large multi-center study taking place in many states as well as in centers in Canada, Australia, New Zealand, Netherlands, and Switzerland.

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

This Phase I study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of 17-N-allylamino-17-demethoxygeldanamycin in treating young patients who have recurrent or refractory leukemia or selected solid tumors, including osteosarcoma.  Patients receive 17-N-allylamino-17-demethoxygeldanamycin (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.

Temozolomide and O6-Benzylguanine for Treating Childhood Cancers

This Phase I study is currently recruiting patients.  This study will investigate the combined use of temozolomide (TMZ) and O6-benzylguanine (O6BG) for treating cancer. TMZ is an anti-cancer drug approved to treat certain brain tumors in adults. TMZ loses its effectiveness over time because a protein called AGT makes the tumor resistant to the drug. O6BG inactivates AGT and, therefore, may prolong TMZ's effectiveness.  Children and young adults under age 21 with various types of cancer, including osteosarcoma, for whom standard treatment was not successful may be eligible for this study.  Participants will receive TMZ capsules by mouth and an intravenous infusion of O6BG 5 days in a row every month for up to 12 months. Blood will be drawn on days 3 and 5 of the first course of treatment to measure AGT levels. Also on day 5 of the first treatment course, 16 blood samples (1 teaspoon each) will be taken over a 48-hour period to study how the two drugs work in the body. If possible, a heparin lock will be placed in the vein to avoid having multiple needle sticks. A tissue biopsy (removal of a small piece of tumor) may be taken if the tumor is close to the skin and not near a vital organ. The sample will be used to evaluate the effect of O6BG on AGT levels.  A total of 48 patients will be recruited.  This study is being conducted at the National Cancer Institute (NCI), Bethesda, Maryland.

Irinotecan in Treating Children With Refractory Solid Tumors

This Phase II study is currently recruiting patients.  The purpose of the study is to study the effectiveness of irinotecan in treating children who have refractory solid tumors, including osteosarcoma.  Patients are stratified according to type of solid tumor or brain tumor.  Patients receive irinotecan IV over 60 minutes on days 1-5.  Treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.  A total of 225 patients will be accrued for this study.  Patients 1 to 21 years of age are eligible.  This is a large multi-center study taking place in many states as well as in Australia, Canada, Netherlands, New Zealand, and Switzerland.

Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors

This Phase II study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy in treating children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors, including osteosarcoma.  Patients are stratified according to risk group (standard vs. high).  The treatment outline for this study is as follows:

Standard-risk patients:

Initial chemotherapy: Patients receive vincristine IV on day 1 for weeks 1-7. Patients also receive dactinomycin IV on day 1 and ifosfamide IV over 1 hour on days 1-3 of week 1. Patients then receive carboplatin IV over 1 hour and epirubicin IV over 6 hours on day 1 of week 4. Patients then receive ifosfamide IV over 1 hour and etoposide IV over 4 hours on days 1-3 of week 7. Treatment repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. After the second course, patients with less than 50% partial response (PR) are removed from study. Patients with parameningeal disease undergo radiotherapy 5 days a week for about 8 weeks beginning at week 9.

Maintenance chemotherapy: Patients receive cyclophosphamide IV over 1 hour, vincristine IV, and dactinomycin IV on day 1. Treatment repeats every 3 weeks for 9 courses in the absence of disease progression or unacceptable toxicity. Patients who remain in PR at week 17 undergo radiotherapy for about 9 weeks beginning at week 18.

High-risk patients:

Initial chemotherapy: Patients receive window study drug carboplatin IV over 1 hour or doxorubicin on day 1. Treatment repeats every 3 weeks for 2 courses. Patients receive high-dose cyclophosphamide IV over 1 hour on days 1-3 of week 7. Beginning on day 8, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) daily until day 13. Patients may undergo peripheral blood stem cell (PBSC) collection. Patients receive high-dose etoposide IV over 24 hours on days 15-17. Beginning on day 22, patients receive G-CSF IV or SC daily until day 27. Patients receive high-dose cyclophosphamide IV over 1 hour on days 29-31. Beginning on day 36, patients receive G-CSF IV or SC daily until day 42. Patients may undergo PBSC collection if not previously performed. Patients who achieve complete response (CR) are removed from study. Patients receive high-dose carboplatin IV over 1 hour on days 44-48. Patients undergo PBSC reinfusion on day 52. Beginning on day 55, patients receive G-CSF IV or SC daily until blood counts recover.

Maintenance chemotherapy: Patients receive maintenance chemotherapy comprising cyclophosphamide, vincristine, and dactinomycin in the same manner as the standard-risk patients. Patients with parameningeal disease and those not achieving CR undergo radiotherapy beginning at week 17. Patients achieving CR, unless metastatic disease is resected, undergo radiotherapy beginning on week 15.

A total of 8-30 standard-risk patients and 15-75 high-risk patients will be accrued for this study within 4-5 years.  Patients 6 months to 17 years of age are eligible.  This study is being conducted at centers in France, Ireland, and the United Kingdom.

Study of AP23573, an mTOR Inhibitor, in Patients with Advanced Sarcoma

This Phase II study is currently recruiting patients.  The primary purpose of this study is to assess the efficacy of AP23573 in patients with advanced sarcomas, including osteosarcoma.  AP23573 is being developed by Ariad Pharmaceuticals, and it targets the cell-signaling protein mTor.  Ariad’s preclinical studies in animal models in a wide variety of solid tumors have shown anticancer activity, including cancer cell starvation, tumor shrinkage, and controlling tumor blood supply through its effects on VEGF.  AP23573 will be administered once daily for 5 consecutive days every two weeks.  The secondary objectives of the study are to assess the safety & tolerability of this study drug regimen; to evaluate secondary efficacy endpoints, such as time to tumor progression, progression-free survival and duration of response; and to examine AP23573 blood levels and experimental parameters that may predict or indicate response to mTOR inhibition, such as effects on plasma VEGF levels and markers of tumoral PI3K/mTOR-pathway activity.  The expected total enrollment is 176 patients.  Patients 15 years of age and older are eligible.  This study is being conducted at cancer centers in California and Texas.

P-glycoprotein Antagonist, Tariquidar, in Combination with Doxorubicin (Adriamycin), Vinorelbine (Navelbine), or Docetaxel to Treat Children with Solid Tumors

This Phase I study is currently recruiting patients.  This study will examine the safety and side effects of tariquidar in children and adolescents with cancer and test whether it can improve current anticancer drug treatments.  Studies have found that a protein (P-glycoprotein) on some cancer cells pumps anticancer drugs out of the cells, reducing treatment effectiveness.  In laboratory tests, an experimental drug called tariquidar has blocked pumping by this protein. Tariquidar is being used in this study to try to increase amounts of the anticancer drugs vinorelbine (Navelbinea), doxorubicin (Adriamycin) or docetaxel (Taxotere) in cancer cells.  Patients between 2 and 18 years of age with solid tumors, including osteosarcoma, who have relapsed or who do not respond to frontline therapy and have no other treatment options may be eligible for this study.  Participants will receive tariquidar plus either doxorubicin, vinorelbine or docetaxel, depending on the type of cancer, previous treatments, and side effects of prior treatment.  Treatment will be given in 21-day cycles for no more than eight cycles.  The expected total enrollment is 36 patients.  This study is taking place at the National Cancer Institute, Bethesda, Maryland.

A Phase I Study of Single Agent OSI-774 (Tarceva) Followed by OSI-774 with Temozolomide for Patients with Selected Recurrent/Refractory Solid Tumors, Including Brain Tumors

This Phase I study is currently recruiting patients.  The epidermal growth factor receptor (EGFR/ErbB2) tyrosine kinase signal transduction pathway has an important role in cell proliferation, motility, adhesion, invasion, survival, and angiogenesis. Dysregulation of this pathway contributes to the development and progression of malignancies. ErbB1 or ErbB2 receptor expression or over-expression has been observed in osteosarcomas, and other cancers.  OSI-774 is an orally bioavailable epidermal growth factor (EGFR/ErbB2) receptor tyrosine kinase inhibitor.  Antitumor activity of OSI-774 has been seen in a wide range of human tumors.   In adult Phase I and II trials, OSI-774 had promising clinical activity and the daily dosing (150 to 200mg/day) schedule was well tolerated.  In laboratory models, EGFR inhibitors enhance the activity of standard cytotoxic agents, including temozolomide.  Temozolomide, an oral alkylating agent, has a broad spectrum of antitumor activity.  In this study, OSI-774 oral solution will be administered once daily for 28 days.   Patients will be evaluated for toxicity attributable to OSI-774. In the absence of dose limiting toxicity during the initial 28 days, patients will start combination therapy with temozolomide and OSI-774 oral solution once daily for 28 days. In the absence of dose limiting toxicity, the dose of temozolomide may be escalated in subsequent cycles. No intrapatient dose escalation of OSI-774 is permitted. OSI-774 pharmacokinetics will be done on days 1, 2, 3, 10 and 11 of OSI-774 alone and days 5 and 6 of the combination phase of the study. The expression and activation of ErbB pathway and its downstream signaling mediators (phospho-AKT and phospho-p70s6kp) will be determined in archival tissue.  The total expected enrollment is 74 patients.  Patients under 22 years of age are eligible.  This study is taking place at the National Cancer Institute, Bethesda, Maryland.

High-Dose Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Advanced Cancer

This Phase I study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy plus peripheral stem cell transplantation in treating patients who have advanced cancers.  Osteosarcoma patients who are ineligible for or refused participation in higher priority protocols are eligible for this study.  At least 4 weeks prior to chemotherapy, patients undergo stem cell collection following filgrastim (G-CSF) mobilization. Sufficient stem cells to support 2 courses of chemotherapy are required.  Autologous bone marrow is collected as an adjuvant if stem cell harvest is inadequate.  Patients then receive high dose cisplatin, etoposide, and cyclophosphamide over 10 days, followed the next day by infusion of one fourth of the allotted stem cells, with the remaining allotment infused 2 days later. G-CSF is given for granulocyte support.  Beginning no sooner than 14 weeks from the start of the first course of chemotherapy, stable and responding patients receive high dose paclitaxel, carboplatin, and ifosfamide over 5 days, followed 2 days later with one-fourth of the allotted stem cells, with the remaining allotment infused the following day. G-CSF is given for granulocyte support. Groups of 3-6 patients are treated with escalating doses of paclitaxel until the maximum tolerated dose for this regimen is determined.  Patients are followed monthly for 1 year, every 3 months for 1 year, then as needed at the physician's discretion for at least 5 years.  Three to six patients will be entered at each dose of paclitaxel studied.  Patients 18 to 55 years of age are eligible.  This study is taking place at the City of Hope Comprehensive Cancer Center, Duarte, California.

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

This Phase I study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of 17-N-allylamino-17-demethoxygeldanamycin in treating patients who have advanced epithelial cancer, malignant lymphoma, or sarcoma.  This is a dose-escalation study. Patients receive treatment according to 1 of 2 schedules.

	Schedule B: Patients receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 1-2 hours twice weekly for 3 weeks. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
	Schedule C: Patients receive 17-AAG IV over 1-2 hours twice weekly for 2 weeks. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

In both schedules, 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 6 patients experience dose-limiting toxicity.  At least 6 patients receive treatment at the MTD.  A maximum of 60 patients will be accrued for this study.  Patients 18 years of age and older are eligible for this study.  This study is taking place at the Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.

Combination Chemotherapy Plus Filgrastim in Treating Patients With Advanced Solid Tumors

This Phase I study is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combination chemotherapy plus filgrastim in treating patients who have advanced solid tumors, including sarcomas.  This is a dose-escalation study of docetaxel.  Patients receive docetaxel IV over 1 hour followed by gemcitabine IV over 30 minutes on day 1. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 2 and continuing until blood counts recover. Treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of docetaxel 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.  Fatigue is assessed at baseline and then at weeks 2, 5, 7, and 9 during therapy.  A maximum of 30 patients will be accrued for this study within 15-22 months.  Patients 18 years of age and older are eligible.  This study is taking place at the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Arsenic Trioxide in Treating Patients With Advanced Neuroblastoma or Other Childhood Solid Tumors

This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of arsenic trioxide in treating children who have advanced neuroblastoma or other solid tumors, including osteosarcoma.    Patients are stratified according to type of disease.  Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 and 8-12. Treatment repeats every 28 days for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.  Patients are followed every 2-3 months for 1 year and then annually thereafter.  A total of 45-120 patients (15-40 per stratum) will be accrued for this study.  Patients 40 years of age and under are eligible.  This study is taking place at Memorial Sloan-Kettering Cancer Center, New York, NY.

ABT-751 in Treating Young Patients With Refractory Solid Tumors

This Phase I trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of ABT-751 in treating young patients who have refractory solid tumors, including osteosarcoma.  This is an open-label, dose-escalation study of 2 different schedules of ABT-751. Patients are assigned to 1 of 2 dosing schedules.  In Schedule 1: Patients receive oral ABT-751 once daily on days 1-7. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.  In Schedule 2: Patients receive oral ABT-751 once daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. On each schedule, cohorts of 3-6 patients receive escalating doses of ABT-751 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 9 patients (a minimum of 3 patients age 11 and under and 3 patients age 12 to 18) are treated at the MTD.  A maximum of 48 patients (24 per dosing schedule) will be accrued for this study.  Patients 18 years of age and under are eligible.  This study is being conducted at centers in Illinois, Maryland, and Pennsylvania.

Thalidomide and Docetaxel in Treating Patients With Advanced Cancer

This Phase I trial is currently recruiting patients.  The investigators of this study believe that thalidomide may stop the growth of cancer by stopping blood flow to the tumor. Docetaxel is a widely used chemotherapy agent.  Combining thalidomide with docetaxel may kill more tumor cells.  Thus, the purpose of this trial is to study the effectiveness of combining thalidomide with docetaxel in treating patients who have advanced cancer.  Patients with any type of solid tumor including sarcoma are eligible for this study.  This is a dose-escalation study.  Patients receive oral thalidomide twice daily and docetaxel IV over 30 minutes once weekly. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of docetaxel and thalidomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2 of 6 patients experience dose-limiting toxicity.  A total of 3-30 patients will be accrued for this study.  Patients 18 years of age and older are eligible.  This study is taking place at the Ireland Cancer Center at University Hospitals of Cleveland and Case Western Reserve University, Cleveland, Ohio.

Erlotinib and Temozolomide in Treating Young Patients With Recurrent or Refractory Solid Tumors

This Phase I trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of combining erlotinib with temozolomide in treating young patients who have recurrent or refractory solid tumors, including osteogenic sarcoma.  This is a dose-escalation study of erlotinib. Patients are stratified according to pretreatment (heavily pretreated vs. less heavily pretreated).  Patients receive oral erlotinib once daily on days 1-28. Beginning with course 2, patients also receive oral temozolomide once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.  Cohorts of 3-6 patients receive escalating doses of erlotinib during course 1 only 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 9-24 patients will be accrued for this study.  Patients 21 years of age and under are eligible.  This is a large multi-center study taking place in many states as well as in Canada.

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

This Phase I trial is currently recruiting patients.  Radiolabeled monoclonal antibodies can locate tumor cells and deliver radioactive tumor-killing substances, such as radioactive iodine, to them without harming normal cells.  The purpose of this trial is to study the effectiveness of radiolabeled monoclonal antibody therapy in treating patients who have refractory, recurrent, or advanced CNS or leptomeningeal cancer.  Osteosarcoma patients are eligible.  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.  Patients of any age are eligible.  The study is being conducted at Memorial Sloan-Kettering Cancer Center, New York, NY.

Combination Chemotherapy With or Without Hyperthermia Therapy in Treating Patients With Soft Tissue Sarcoma

This Phase III trial is currently recruiting patients.  Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not known whether receiving chemotherapy plus hyperthermia is more effective than receiving chemotherapy alone in treating patients with soft tissue sarcoma.  Thus, the purpose of this trial is to compare the effectiveness of combination chemotherapy with or without hyperthermia therapy in treating patients with soft tissue sarcoma, including osteosarcoma.  Patients are stratified according to risk category and disease site (extremity vs. nonextremity). Patients are randomized to one of two treatment arms.  In Arm I: Patients receive etoposide IV over 30 minutes on days 1 and 4, ifosfamide IV over 60 minutes on days 1-4, and doxorubicin IV over 30 minutes on day 1. Treatment continues every 21 days for a total of 4 courses. Patients also undergo regional hyperthermia.  In Arm II: Patients receive chemotherapy alone as in arm I. Patients in both arms undergo definitive surgery 4-6 weeks after chemotherapy. Patients also undergo radiotherapy beginning 4-6 weeks after surgery. After completion of surgery and radiotherapy, patients with non-resectable tumors showing no disease progression receive an additional 4 courses of chemotherapy with or without regional hyperthermia according to above treatment schedule.  A total of 340 patients (170 patients per arm) will be accrued for this study.  Patients 18 to 70 years of age are eligible.  This study is being conducted at several centers in Germany.

Oxaliplatin in Treating Young Patients With Recurrent Solid Tumors That Have Not Responded to Previous Treatment

This Phase II trial is currently recruiting patients.  The purpose of this trial is to study the effectiveness of oxaliplatin in treating young patients with recurrent solid tumors, including osteosarcoma, that have not responded to previous treatment.  Patients are stratified according to disease type.  Patients receive oxaliplatin IV over 2 hours on day 1. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.  A total of 180 patients will be accrued for this study.  Patients up to 21 years of age are eligible.  This is a large multi-center study taking place in many states as well as in Austria, Canada, Netherlands, New Zealand, and Switzerland.

BMS-247550 to Treat Children with Solid Tumors

This Phase I trial is currently recruiting patients.  The experimental anticancer drug BMS-247550 belongs to a class of drugs called epothilones. These drugs are similar to another class called taxanes, which includes paclitaxel (Taxol) and docetaxel (Taxotere). The epothilones are able to kill cancer cells that are resistant to Taxol.  This study will determine the highest dose of BMS-247550 that can be given safely to children. It will examine how the body handles the drug, its side effects and its effect on tumors.  Participants will receive BMS-247550 intravenously over a 60-minute period for 5 consecutive days in 21- to 28-day cycles (i.e., 5 days of drug treatment followed by 15 to 22 days without drug, depending on the amount of time needed to recover from the drug side effects). The drug dose will be increased in successive small groups of patients, if the side effects at the previous dose are acceptable, until the optimum dose is achieved.  Patients may continue treatment indefinitely unless their cancer worsens or they develop side effects that persist for more than 2 weeks.  The total expected enrollment is 30 patients.  Patients 2 to 18 years of age are eligible.  This study is taking place at the National Cancer Institute, Bethesda, Maryland.

Phase I Trial of ABT-751 in Children with Solid Tumors

This Phase I study is currently recruiting patients.  This study will determine the side effects and maximum tolerated dose of the experimental drug ABT-751 that can be safely given to children and young adults with solid tumors.  ABT-751 belongs to a new class of anticancer drugs that hamper the replication of cancer cells.  It works by binding to a protein called tubulin.  Other drugs that work this way include vincristine, vinblastine, vinorelbine, paclitaxel, and docetaxel.  In laboratory studies, ABT-751 kills cancer cells that are resistant to vincristine and paclitaxel.  Patients up to 18 years of age with solid tumors, including osteosarcoma, whose disease has relapsed, or whose tumor no longer responds to standard treatment, may be eligible for this study.  Participants will take one ABT-751 capsule a day for 7 days each treatment cycle.  A treatment cycle will be 21 to 28 days, depending on how long it takes the patient to recover from the drug side effects.  The drug dose will be increased gradually in successive groups of patients if side effects of the previous dose were acceptable.  Patients may continue treatment unless their disease worsens with ABT-751 or irreversible side effects occur.  Expected total enrollment is 48 patients.  This study is being conducted at the National Cancer Institute, Bethesda, Maryland.

Not Yet Recruiting Osteosarcoma Clinical Trial

Gemcitabine and Docetaxel in Treating Patients With Recurrent Osteosarcoma or Ewing's Sarcoma or Unresectable or Locally Recurrent Chondrosarcoma

This Phase II trial is not yet open for patient recruitment.  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.  The location of this study has not yet been identified.

Additional Clinical Trials

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients

This concluded Phase II trial evaluated the efficacy, safety, and pharmacokinetics of ecteinascidin-743 (ET-743) in pretreated advanced soft tissue sarcoma patients. Patients received ET-743 every 3 weeks. The patients consisted of 30 women and 24 men, with a median age of 48 years; 41% had leiomyosarcoma and 93% had documented progressive disease at study entry. Fifty-two patients were assessable for response. There was two partial responses, four minor responses, and nine with stable disease (> or = 6 months). Three patients were rendered tumor free after surgery.  The median progression-free survival was 1.9 months (range: 0.69 to 17.90 months); 24% of patients were progression free at 6 months. The median survival was 12.8 months, with 30% of patients alive at 2 years.  Four patients withdrew because of treatment-related toxicity. Two treatment-related deaths occurred that were probably related to protocol eligibility violations. The trial concluded that with a 4% overall response rate and an 11% rate of third-party-verified tumor regression (overall response rate + minor response), ET-743 had a 24% 6-month disease progression control rate, confirming evidence of anti-tumoral activity and a manageable safety profile in patients experiencing disease progression with pretreated soft tissue sarcoma.

Vertex and Merck Announce First Clinical Study for Aurora Kinase Inhibitor, VX-680, in Solid Tumor Cancers [No longer available on the web 10/2005]

Merck & Co., Inc. and Vertex Pharmaceuticals Inc. announced on January 6, 2005 that they have begun a Phase I clinical study for VX-680, a small molecule inhibitor of Aurora kinases, in patients with solid tumor cancers.  Aurora kinases are enzymes that are believed to play multiple roles in the development and progression of cancer by acting as regulators of cell proliferation by transforming normal cells into cancer cells, and by down-regulating p53, one of the body's natural tumor suppressors.  Aurora kinases have been implicated in many cancers.  This new Phase I open-label, dose-escalation study is designed to evaluate the safety and tolerability of VX-680 when administered in multiple cycles to patients with solid tumors refractory to prior chemotherapy treatment.  Merck and Vertex also plan to initiate additional Phase I studies of VX-680 later this year.

V2N1 ESUN Copyright © 2005 Liddy Shriver Sarcoma Initiative