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Abstracts by Tom Swartz
[Editor's Note: Because the Clinical Trial News column is so highly accessed, we have reduced the need for you to "search" back issues of ESUN to locate clinical study information. We have created three separate webpages where all of the clinical trial information that we have published in ESUN to date has been collected. You can read about these changes in the editorial, Changes Made, in the October 2006 issue of ESUN. With the addition of the clinical trials described in this issue of ESUN, we now have over 185 clinical trials listed on our website.]
Currently Accepting Eligible Patients (not previously published in ESUN)
This Phase II trial is currently recruiting patients. REOLYSIN is an unmodified oncolytic reovirus which replicates selectively in ras transformed cells causing cell lysis. Activating mutations in ras or mutations in oncogenes signaling through the ras pathway may occur in as many as 80% of human tumors. Such mutations have been described in many of the common sarcomas of childhood and adults. REOLYSIN has demonstrated excellent anti-tumor activity in vitro and in vivo in childhood sarcoma cell lines. Further supporting the development of REOLYSIN in the context of sarcomas as detailed in this study, is the fact that sarcomas resistant or refractory to conventional chemotherapy may remain clinically responsive to viral therapy. Sarcoma patients with pulmonary metastases may be especially suitable for studies with REOLYSIN due to rapid selective uptake of the virus by the lungs. Thus, this Phase 2 study is designed to characterize the efficacy and safety of REOLYSIN given intravenously over 5 days every 4 weeks in patients with bone and soft tissue sarcomas metastatic to the lung. Safety data, including laboratory parameters and adverse events, will be collected for all patients in order to determine the toxicity and reversibility of toxicity of REOLYSIN therapy. Response will be assessed using radiographic imaging every 2 cycles of therapy. The total expected enrollment is 52 patients. Patients 16 years of age and older are eligible. This trial is taking place at the University of Michigan Medical School, Ann Arbor, Michigan, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, New York, and the Institute of Drug Development, Cancer Therapy Research Center, San Antonio, Texas.
Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies This Phase I trial is currently recruiting patients. The human p53 tumor suppressor protein is overexpressed in a wide range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal proliferation and exhibits a longer half-life than the wild-type protein, allowing for its accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation and aggression and is associated with lower overall survival rates and resistance to chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for a considerable number of human malignancies and represents a good target for immunotherapeutics.
However, p53 cannot be used as a target for antibodies because it is not displayed independently on the cell surface. Instead, the p53 protein is processed intracellularly into peptide fragments that are then displayed on the cell surface in the context of MHC. These peptide/MHC complexes are recognized by T-cells via their T-cell receptors (TCRs). Recently it has been confirmed that the peptide fragment is significantly elevated in a wide range of human tumor tissues. Targeted approaches to concentrate therapeutic cytokines at the tumor sites that express p53 could provide considerable advantages over current treatment.
Interleukin-2 (IL-2) is a well-characterized growth factor for immune effector cells which play critical roles in tumor control and rejection. A recombinant human IL-2 has been approved for treating metastatic melanoma and renal cell carcinoma. However, the major drawback of IL-2 therapy is its severe systemic toxicity. As a result, use of high dose IL-2 is limited to specialized programs with experienced personnel and it is generally offered to patients who are responsive and have excellent organ function. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2 or reduce its toxicity without compromising clinical benefits.
The drug involved in this study, ALT-801, is a biologic compound composed of interleukin-2 (IL-2) genetically fused to a humanized soluble T-cell receptor directed against the p53-derived antigen. Thus, the purpose of this study is to evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor sites that overexpress p53 results in clinical benefits. The study is open to patients with locally advanced or metastatic malignancies and HLA-A2.1/p53 positive.
The study drug will be administered by bolus intravenous infusion in an in-patient hospital setting under the supervision of a qualified physician experienced in the use of anti-cancer agents including high dose IL-2. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. There are two treatment cycles. For each treatment cycle, patients will be admitted to the hospital, remain in the hospital during the study drug infusion period, and be discharged from the hospital the day after the last infusion at the Principal Investigator’s discretion. There is a 10-day resting period between the treatment cycles. Tumor assessments will be done at weeks 7 and 11 after starting the study drug. The total expected enrollment is 46 patients. Patients 18 years of age and older are eligible. The trial is taking place at the H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida.
Phase 1 Study Of Anti-IGF-IR CP-751,871 In Patients With Solid Tumors This Phase I trial is currently recruiting patients. This study is testing the safety and tolerability of anti-IGF-IR CP-751,871 in patients with solid tumors, currently enrolling adult patients with rhabdomyosarcoma and Ewing's family of tumors, including synovial sarcoma and desmoplastic round small cell tumors. The total expected enrollment is 48 patients. Patients 18 years of age and older are eligible. This trial is taking place at Pfizer Investigational Sites in Ann Arbor, Michigan, Rochester, Minnesota, Sutton, Surrey, United Kingdom.
Sunitinib in Treating Patients With Metastatic, Locally Advanced, or Locally Recurrent Sarcomas This Phase II trial is currently recruiting patients. Sunitinib 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. This trial is studying how well sunitinib works in treating patients with metastatic, locally advanced, or locally recurrent sarcomas. This is a multicenter study. Patients are stratified by neoplastic subtype (vascular connective tissue neoplasms, leiomyosarcoma, dermatofibrosarcoma protuberans, chordoma, or desmoid tumors vs. high-grade undifferentiated pleomorphic sarcoma [i.e., malignant fibrous histiocytoma (including myxofibrosarcoma)], or other nongastrointestinal connective tissue tumors [including carcinosarcomas]). Patients receive oral sunitinib malate once daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically. A total of 82 patients will be accrued for this study. Patients 18 years of age and older are eligible. This trial is taking place at the Dana-Farber Cancer Institute, Boston, Massachusetts and Memorial Sloan-Kettering Cancer Center, New York, New York.
Stress Management Therapy in Patients Receiving Chemotherapy for Cancer This trial is currently recruiting patients. A stress-management program may improve quality of life and reduce anxiety and depression in patients receiving chemotherapy for cancer. This randomized clinical trial is studying how well stress management therapy works in patients receiving chemotherapy for cancer. This is a randomized, multicenter study. Patients are stratified according to participating center, use of psychotropic drugs (yes vs. no), and ethnicity (Hispanic vs. non-Hispanic). Patients are randomized to 1 of 2 arms.
Patients complete questionnaires to assess mood, quality of life, and other factors at baseline and before chemotherapy courses 2, 3, and 4. A total of 442 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, the District of Columbia, Illinois, Louisiana, Michigan, Minnesota, Missouri, New Jersey, New York, North Carolina, North Dakota, Ohio, Texas, and Washington.
Aerosol L9-NC and Temozolomide in Ewing’s Sarcoma This Phase I/II trial is currently recruiting patients. L9-NC and temozolomide each work by blocking certain tumor cell functions, which can keep tumor cells from growing. The purpose of this trial is to: (1) determine the feasibility and toxicity profile of administering liposomal 9-Nitro-20-(S)-Camptothecin (L9-NC) by aerosol alone and in combination with temozolomide; and (2) determine the effectiveness of L9-NC given by aerosol in combination with temozolomide in patients with solid tumors involving the lungs.
If you are found to be eligible to take part in this study, you will be given the L9-NC aerosol (an inhaled spray) by mouth through a face mask for Cycle 1 of therapy. You will receive L9-NC over about 30 minutes once a day, for 5 days in a row. This will be done for 2 weeks. Doctors will then monitor you for safety for another 2 weeks after treatment. A treatment cycle lasts for 4 weeks. Your first L9-NC aerosol treatment, during Cycle 1, will be given at M. D. Anderson. You may receive the rest of your treatments at home, if you experienced no bad side effects with the first aerosol treatment.
During Cycle 2 of therapy, if you have not experienced any intolerable side effects, you will be given temozolomide. You will receive temozolomide by mouth once a day, for 5 days in a row, during the first week of each cycle. You will also continue to receive the L9-NC aerosol over about 30 minutes once a day, for 5 days in a row, for 2 weeks. Doctors will then monitor you for safety for another 2 weeks after treatment.
During Cycle 3 of therapy, if you have not experienced any intolerable side effects, you will continue to be given temozolomide by mouth once a day, for 5 days in a row, during the first week of each cycle. You will receive the L9-NC aerosol twice a day, about 12 hours apart, over about 30 minutes, for 5 days in a row, for 2 weeks. If you experienced any bad side effects during Cycle 2, your dose of temozolomide will be decreased, and you will continue to receive L9-NC aerosol once a day (instead of twice a day), for 5 days in a row, for 2 weeks.
For all further cycles of treatment, if you experienced any bad side effects during Cycle 3, you will receive L9-NC only once a day, instead of twice a day. If you are already receiving L9-NC only once a day, and you experience intolerable side effects in Cycle 3, you will be taken off this study.
You will be shown how to do spirometry (a lung test that measures how much and how fast air moves out of the lungs) to monitor the safety of your therapy. You will be asked to do this after each treatment cycle, for the first 2 cycles. If your dose of L9-NC is increased to twice a day, you will also be asked to do spirometry after the second dose of the day during Cycle 3. For future cycles, you will be asked to do spirometry after the last dose of L9-NC, on the first day of each week of treatment. The results of spirometry will need to be sent to M. D. Anderson by telephone, after each test. The results will be sent electronically. They will be reviewed every day after they are received, and you will be contacted if there are abnormal results. Your doctor may also perform additional spirometry as needed.
You will be examined by a doctor before the second and third cycle of therapy (every 4 weeks). You will have blood drawn (about 2 tablespoons) every week during the first 2 to 3 cycles of therapy. After Cycle 3 of therapy, blood tests (about 2 tablespoons) will be done before each cycle of therapy. Chest x-rays, CT chest scans, and any other imaging studies, as done at the beginning of this study, will be done to measure your disease and will be repeated after every 3 cycles of therapy. You will also have a breathing function test, if the doctor thinks it is necessary.
If your tumor size decreases during this treatment, you may have other therapy performed, such as surgery, radiation, or radiofrequency ablation, outside of this study. If the treatment in this study alone, or in combination with other therapy, results in complete disappearance of your disease, your treatment on this study may continue for up to 6 more cycles. You will be taken off this study if your disease gets worse or you experience any intolerable side effects. If you are taken off this study for intolerable side effects, you will be followed-up for 30 days after treatment ends or until your side effects go away. If you have a complete remission, chest x-rays, CT chest scans, and any other imaging studies, as done at the beginning of this study, will be done to look for disease about every 3 months after completion of treatment.
Up to 40 patients will take part in this study. Patients 10 years of age and older are eligible. This trial is taking place at M.D. Anderson Cancer Center, Houston, Texas.
The title, description, and location of Clinical Trial NTC00276302 (which previously appeared in ESUN) has changed as follows. This Phase I trial is currently recruiting patients. IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90’s role in the cell is to control the proper folding, function, and viability of various “client” proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas (STS), there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies. Thus, the purpose of this trial is to determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies, and to recommend a dose for subsequent studies of IPI-504. The treatment protocol is not outlined. The total expected enrollment is 40 patients. Patients 18 years of age and older are eligible. This trial is taking place at Dana-Farber Cancer Institute, Boston, Massachusetts, University of Michigan Hospitals, Ann Arbor, Michigan, and Premiere Oncology, Santa Monica, California.
Not Yet Recruiting Patients (not previously published in ESUN)
There are no entries in this category for the April 2007 Issue of ESUN.
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