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Sponsors and Collaborators: |
Northern California Melanoma Center Pfizer Schering-Plough |
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Information provided by: | Northern California Melanoma Center |
ClinicalTrials.gov Identifier: | NCT00304200 |
This study is designed to evaluate the safety and appropriate dose of the combination of Temodar and Sutent as first-line therapy for patients with metastatic malignant melanoma (Phase 1). Once the safety and appropriate dose is determined, additional patients will be studied at that dose to determine if there is clinical benefit as determined by the primary end-point of progression-free survival (PFS) at 6 months and additional secondary endpoints (Phase II).
Condition | Intervention | Phase |
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Metastatic Malignant Melanoma |
Drug: Temodar (temozolomide) Drug: Sutent (SU11248) |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study |
Official Title: | Temodar and Sutent as Therapy for Patients With Malignant Melanoma, a Phase I/II Study |
Estimated Enrollment: | 62 |
Study Start Date: | March 2006 |
Estimated Study Completion Date: | April 2008 |
Patients with unresectable metastatic melanoma have a dismal prognosis. The disease responds poorly to currently available chemotherapies and biological agents. The median survival in this patient population is 6 – 10 months and has not improved significantly in decades. The FDA approved DTIC in 1975 and high dose intravenous bolus rIL-2 in 1998 and these are the only agents approved for therapy of patients with metastatic melanoma.
In a Phase III trial reported in 2000, temozolomide (Temodar, Schering-Plough) demonstrated equivalent overall survival to DTIC in patients with metastatic melanoma, and had the advantages of providing improved progression-free survival, ease of administration (oral), and crossing the blood-brain barrier. Temozolomide and DTIC are both precursors of an active metabolite, monomethyl triazenoimidazole carboxamide (MTIC). SU11248 (Sutent, Pfizer) is a multi-targeted receptor tyrosine kinase inhibitor which targets 3 distinct vascular endothelial growth factor receptor (VEGFR-1, -2, and -3), platelet-derived growth factor receptor alpha and beta (PDGFR-α and -β), KIT receptor tyrosine kinases, and fms-related tyrosine kinase 3/Flk2 (FLT3). Although other angiogenic factors have been identified, VEGF is the most potent and specific regulator of angiogenesis and SU11248 targets not just one, but all 3 VEGF signaling pathways. Dacarbazine (DTIC) causes transcriptional up-regulation of VEGF in melanoma cells and this has been postulated as a possible mechanism of escape from chemotherapy efficacy. Temozolomide, which acts through the same metabolite, MTIC, would be expected to have the same activity. PDGFR-α and -β are important new targets in tumor cell proliferation and angiogenesis. PDGF signaling pathways have been implicated in the development and growth of solid tumors. Inhibition of PDGF receptors has been shown to inhibit angiogenesis, tumor vascular maturation and maintenance, and tumor cell proliferation – inducing tumor regression. In a murine model, the combination of chemotherapy with VEGF and PDFG receptor inhibitors resulted in a remarkable survival advantage.
The study is an open-label, single arm trial. The patient sample will be approximately 56-62 individuals, males and females 18 years of age or older with measurable metastatic melanoma. Study participants must meet a number of laboratory criteria in order to be admitted into the study. The study duration is expected to be approximately 2 years. Patients will be offered treatment for up to 1 year and are expected to complete a median of 6 cycles of treatment.
An interim analysis of safety will be conducted after completion of treatment of 6 patients in each cohort and a determination will be made as to whether or not to continue to the next cohort according to the specifications in the protocol. If an acceptable dosing regimen is found, the study will proceed to a Phase II portion. Progression-free survival will be determined for the 6 month time point when all patients have completed the study. The study has ≥90% power to detect an increase in the 6-month progression-free survival rate from ≤15%, the result expected for patients receiving available first-line therapy, to ≥35% for patients receiving the combination of temozolomide and SU11248, based on a one group chi-square test with a 0.05 two-sided significance level.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Adequate hematologic, renal and liver function as defined by laboratory values performed within 28 days prior to initiation of dosing.
Exclusion Criteria:
Contact: Sharon Trautvetter, RN | 415-353-6535 | Sharon.Trautvetter@chw.edu |
Contact: Lynn E. Spitler, MD | 415-353-6535 | Lynn.Spitler@chw.edu |
United States, California | |
Northern California Melanoma Center | Recruiting |
San Francisco, California, United States, 94109 | |
Contact: Sharon Trautvetter, RN 415-353-6535 Sharon.Trautvetter@chw.edu | |
Contact: Lynn E. Spitler, MD 4125-353-6535 Lynn.Spitler@chw.edu | |
Principal Investigator: Lynn E Spitler, MD | |
Sub-Investigator: Robert Weber, MD | |
Sub-Investigator: Sharon Trautvetter, RN | |
Northern California Melanoma Center | Not yet recruiting |
San Francisco, California, United States, 94109 | |
Northern California Melanoma Center | Recruiting |
San Francisco, California, United States, 94109 | |
Contact: Sharon Trautvetter, RN 415-353-6535 sharon.trautvetter@chw.edu | |
Principal Investigator: Lynn E Spitler, MD | |
Sub-Investigator: Robert Weber, MD |
Principal Investigator: | Lynn E. Spitler, MD | Northern California Melanoma Center |
Study ID Numbers: | Temodar/Sutent |
Study First Received: | March 12, 2006 |
Last Updated: | March 9, 2007 |
ClinicalTrials.gov Identifier: | NCT00304200 |
Health Authority: | United States: Food and Drug Administration |
Metastatic Malignant Melanoma |
Neuroectodermal Tumors Sunitinib Nevus, Pigmented Neoplasms, Germ Cell and Embryonal Neuroepithelioma |
Nevus Temozolomide Neuroendocrine Tumors Melanoma |
Neoplasms by Histologic Type Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Growth Substances Physiological Effects of Drugs Neoplasms, Nerve Tissue Angiogenesis Inhibitors Pharmacologic Actions |
Neoplasms Therapeutic Uses Nevi and Melanomas Growth Inhibitors Antineoplastic Agents, Alkylating Angiogenesis Modulating Agents Alkylating Agents |