Clinical Trial: Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: A Multicenter, Open Label, Randomized Phase II Trial of the MEK Inhibitor Pimasertib or Dacarbazine in Previously Untreated Subjects With N-Ras Mutated Locally Advanced or Metastatic Malignant
Brief Summary: This is a Phase 2, multicenter, randomized, controlled, open-label trial of pimasertib versus dacarbazine aimed to confirm the activity of pimasertib in previously untreated subjects with N-Ras mutated locally advanced or metastatic malignant cutaneous melanoma by comparing the progression-free survival (PFS) of subjects treated with either pimasertib or dacarbazine and by getting a better understanding of the efficacy, safety, pharmacogenomics (PGx) and their relationship with pimasertib exposure.
Detailed Summary:
Sponsor: EMD Serono
Current Primary Outcome: Progression-free survival (PFS), defined as the first documentation of objective disease progression, according to Response Evaluation Criteria in Solid Tumors (RECIST v.1.1) [ Time Frame: every 6 weeks up to Cycle 13, then every 12 weeks up to 2 years ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Objective response defined as complete or partial tumor response, according to RECIST v.1.1 criteria [ Time Frame: every 6 weeks up to Cycle 13, then every 12 weeks up to 2 years ]
- Disease control defined as the proportion of subjects with complete response, partial response, or stable disease for more than 3 months, according to RECIST v.1.1 criteria [ Time Frame: every 6 weeks up to Cycle 13, then every 12 weeks up to 2 years ]
- Progression-free survival rate at six months from the time of randomization based upon observation of objective disease progression at this time point, according to RECIST v.1.1 criteria [ Time Frame: up to 6 months ]
- Overall survival defined as the time from randomization to death from any cause [ Time Frame: every 6 months up to 2 years ]
- Overall survival rate at 12 months from the time of randomization [ Time Frame: up to 12 months ]
- Change in patient-reported Quality of life (assessed by FACT-Melanoma) from baseline assessment to last assessment prior to objective disease progression, according to RECIST v.1.1 [ Time Frame: Day 1 of every cycle up to 2 years ]
- Number of subjects with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and death [ Time Frame: up to 2 years ]
- Clinically significant changes in safety related to National Cancer Institute- Common Toxicity Criteria Version 4.0 (NCI-CTC v 4.0) and abnormal vital signs [ Time Frame: up to 2 years ]
- Plasma concentration of Pimasertib [ Time Frame: Day 8 and Day 15 of Cycle 1, and Day 1 of Cycle 2 ]
- Gene products and genetic alterations in tumor biopsies [ Time Frame: Day 1 of Cycle 1 ]
- Predictive markers in plasma [ Time Frame: Day 1 of Cycle 1 ]
- Potential genetic variations in genomic deoxyribonucleic acid (gDNA) obtained from Peripheral Blood Mononuclear Cell (PBMC) associated with differences in pharmacokinetic and profile of pimasertib [ Time Frame: Day 1 of Cycle 1 ]
Original Secondary Outcome:
- Objective response defined as complete or partial tumor response, according to RECIST v.1.1 criteria [ Time Frame: every 6 weeks up to Cycle 13, then every 12 weeks up to 2 years ]
- Disease control defined as the proportion of subjects with complete response, partial response, or stable disease for more than 3 months, according to RECIST v.1.1 criteria [ Time Frame: every 6 weeks up to Cycle 13, then every 12 weeks up to 2 years ]
- Progression-free survival rate at six months from the time of randomization based upon objective disease progression, according to RECIST v.1.1 criteria [ Time Frame: up to 6 months ]
- Overall survival defined as the time from randomization to death from any cause [ Time Frame: every 6 months up to 2 years ]
- Overall survival rate at 12 months from the time of randomization [ Time Frame: up to 12 months ]
- Change in patient-reported Quality of life (assessed by FACT-Melanoma) from baseline assessment to last assessment prior to objective disease progression, according to RECIST v.1.1 [ Time Frame: Day 1 of every cycle up to 2 years ]
- Number of subjects with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs) and death [ Time Frame: up to 2 years ]
- Clinically significant changes in safety related to National Cancer Institute- Common Toxicity Criteria Version 4.0 (NCI-CTC v 4.0) and abnormal vital signs [ Time Frame: up to 2 years ]
- Plasma pharmacokinetic parameters of pimasertib [ Time Frame: Day 8 and Day 15 of Cycle 1, and Day 1 of Cycle 2 ]
- Gene products and genetic alterations in tumor biopsies [ Time Frame: Day 1 of Cycle 1 ]
- Predictive markers in plasma [ Time Frame: Day 1 of Cycle 1 ]
- Potential genetic variations in genomic deoxyribonucleic acid (gDNA) obtained from Peripheral Blood Mononuclear Cell (PBMC) associated with differences in pharmacokinetic and profile of pimasertib [ Time Frame: Day 1 of Cycle 1 ]
Information By: EMD Serono
Dates:
Date Received: September 14, 2012
Date Started: December 2012
Date Completion:
Last Updated: February 11, 2016
Last Verified: February 2016