SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report

Report for Clinical Trial NCT02357732

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase I Study of the Anti-PD-1 Antibody Nivolumab in Combination With Dabrafenib and/or Trametinib in Patients With BRAF or NRAS-mutated Metastatic Melanoma

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.

NCT02357732 Metastatic Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

3 Interventions

Name: Nivolumab

Type: Drug

Nivolumab and Dabrafenib Combination (doublets) Nivolumab and Trametinib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)

Name: Trametinib

Type: Drug

Nivolumab and Trametinib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)

Name: Dabrafenib

Type: Drug

Nivolumab and Dabrafenib Combination (doublets) Nivolumab, Dabrafenib and Trametinib Combination (triplet)

Primary Outcomes

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 dosing

Secondary Outcomes

Description: 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 drug
Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment

There is one SNP

SNPs

1 V600E

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 ---


HPO Nodes

HPO:
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Melanoma
Genes 64
RAD51 RAD51C TYR RAD51D CDKN2A KRAS CDKN2B RAF1 CDKN2D MRE11 CYSLTR2 ERCC2 KLLN PTPN11 ERCC3 BRIP1 ERCC4 ERCC5 ERCC6 SF3B1 NRAS MGMT BRCA1 MBTPS2 BRAF ACD BRCA2 PIK3CA CXCR4 CTSC POLH POT1 MC1R MITF WRN CHEK2 HRAS BARD1 NBN AKT1 SLC45A2 GNA11 TRPV3 XPA OCA2 XPC GNAQ PTEN MDM2 TERT DDB2 RNF43 PALLD PALB2 TERF2IP SEC23B TP53 SDHB SDHC SDHD SMAD4 BAP1 CDK4 RAD50