This study evaluates nivolumab in combination drug treatments involving 1) nivolumab and dabrafenib 2) nivolumab and trametinib and 3) nivolumab, dabrafenib and trametinib in patients with BRAF or NRAS-mutated metastatic melanoma.
Name: Nivolumab
Type: DrugNivolumab and Dabrafenib Combination (doublets) Nivolumab and Trametinib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)
Name: Trametinib
Type: DrugNivolumab and Trametinib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)
Name: Dabrafenib
Type: DrugNivolumab and Dabrafenib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)
Description: It is planned to determine the maximum tolerable dose with a modified version of the standard "up and down" (3+3) dose-finding method using cohorts of 3 patients. At the start of the trial, three patients will be placed on dose level 1. The decision rules based on the observed dose limiting toxicities (DLTs) in this and subsequent cohorts are given. Only DLTs observed in a patient during the first cycle (28 days) will be used for the dose escalation decisions. Patients will be considered evaluable for toxicity if they receive 1 complete cycle of therapy, or if they experience DLT; in-evaluable patients will be replaced.
Measure: To determine the Maximally Tolerated Dose and/or Recommended Phase II Dose (RP2D) of nivolumab in combination with dabrafenib and/or trametinib in patients with BRAF- or NRAS-mutated metastatic melanoma Time: The first four weeks of dosingDescription: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) and by the Immune Related Response Criteria. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.
Measure: Antitumor Effects and Immune Related Response Time: Every twelve weeks for three years while on study drugAllocation: Non-Randomized
Parallel Assignment
There is one SNP
Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria.. Inclusion Criteria: - Histologically confirmed metastatic melanoma (Stage IV) or unresectable Stage III melanoma with BRAF V600E/K or NRAS mutations. --- V600E ---
Inclusion Criteria: - Histologically confirmed metastatic melanoma (Stage IV) or unresectable Stage III melanoma with BRAF V600E/K or NRAS mutations. --- V600E ---