SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01682083

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection

This was a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. Subjects were randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.

NCT01682083 Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

3 Interventions

Name: Dabrafenib

Description: Each capsule contained 50 mg or 75 mg of free base (present as the mesylate salt)

Type: Drug

Dabrafenib and trametinib

Name: Trametinib

Description: Each tablet contained 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)

Type: Drug

Dabrafenib and trametinib

Name: Placebos

Description: The placebo capsules and tablets contained the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment

Type: Drug

Dabrafenib and trametinib placebos


Primary Outcomes

Description: Recurrence-free survival was defined as the time from randomization to disease recurrence (local recurrence, distant recurrence, second primary melanoma), or death from any cause.

Measure: Relapse-free Survival (RFS)

Time: Approximately 3.5 years

Secondary Outcomes

Description: Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo

Measure: Overall Survival

Time: approximately 3.5 years

Description: Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo. In the DMFS analysis, the first occurrence of distant metastasis or death (if it occurred before documented recurrence) was counted as an event.

Measure: Distant Metastasis-free Survival

Time: approximately 3.5 years

Description: Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo. In the FFR analysis, local or distant recurrence or a new primary melanoma were counted as events, and patients who died of causes other than melanoma or treatment-related toxicity were censored.

Measure: Freedom From Relapse

Time: approximately 3.5 years

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. --- V600E ---

In the FFR analysis, local or distant recurrence or a new primary melanoma were counted as events, and patients who died of causes other than melanoma or treatment-related toxicity were censored.. Key Inclusion Criteria: - Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. --- V600E ---

- History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) Key Inclusion Criteria: - Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. --- V600E ---

Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma were screened for eligibility. --- 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