Ignite Creation Date:
2024-05-05 @ 4:43 PM
Last Modification Date:
2024-10-26 @ 9:23 AM
Study NCT ID:
NCT00304200
Status:
TERMINATED
Last Update Posted:
2009-02-05
First Post:
2006-03-12
Brief Title:
Temodar and Sutent as Therapy for Melanoma
Sponsor:
Northern California Melanoma Center
Organization:
Northern California Melanoma Center
Study Overview
Official Title:
Temodar and Sutent as Therapy for Patients With Malignant Melanoma a Phase III Study
Status:
TERMINATED
Status Verified Date:
2009-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Funding was inadequate to continue Companies requested closure
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
Detailed Description:
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 3Flk2 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 005 two-sided significance level
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 3Flk2 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 005 two-sided significance level
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None