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Report for Clinical Trial NCT01006980

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine

This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.

NCT01006980 Malignant Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

2 Interventions

Name: Vemurafenib

Description: 960 mg (as 240 mg tables) orally twice daily

Type: Drug

Vemurafenib

Name: Dacarbazine

Description: 1000 mg/m2 intravenously every 3 weeks

Type: Drug

Dacarbazine


Primary Outcomes

Description: An Overall survival event was defined as death due to any cause. The number of participants with overall survival events is reported.

Measure: Overall Survival

Time: From randomization (initiated January 2010) to December 30 2010. Median follow-up time in the vemurafenib group was 3.75 months (range 0.3 to 10.8) and in the dacarbazine group was 2.33 months (range <0.1 to 10.3).

Description: A progression-free survival (PFS) event was defined as disease progression or death due to any cause. Tumor response (progression) was assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria using computed tomography (CT) scans or magnetic resonance imaging (MRI).

Measure: Progression-free Survival

Time: From randomization (initiated January 2010) to December 30 2010.

Secondary Outcomes

Description: BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. Participants who never received study treatment and treated participants without any post-baseline tumor assessments were considered as non-responders. CR: Disappearance of all target lesions, all non-target lesions and no new lesion. Any pathological lymph nodes must have had reduction in the short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion and no new lesion.

Measure: Participants With a Best Overall Response (BOR) of Complete Response or Partial Response

Time: From randomization (initiated January 2010) until December 30, 2010

Description: Duration of response was defined as the time between the date of the earliest qualifying response and the date of disease progression or death due to any cause. Duration of response was calculated only for participants who had a best overall response of Complete Response or Partial Response and was estimated using the Kaplan-Meier method.

Measure: Duration of Response

Time: From randomization (initiated in January 2010) until December 30, 2010.

Description: Time to response was defined as the time from randomization to confirmed response (complete response or partial response).

Measure: Time to Confirmed Response

Time: From randomization (initiated January 2010) until December 30, 2010.

Description: Treatment failure was defined as a secondary endpoint in the protocol, defined as death, disease progression or premature withdrawal of study treatment. This endpoint was not included in the Statistical analysis plan; therefore no analyses of time to treatment failure were performed.

Measure: Time to Treatment Failure

Time: approximately 3 years

Description: The intensity of AEs was graded according to the NCI Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a five-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening and Death). A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution, for example is life-threatening, requires hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or requires intervention to prevent one or other of the outcomes listed above.

Measure: Number of Participants With Adverse Events (AEs)

Time: From randomization (initiated January 2010) until December 30, 2010.

Description: The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.

Measure: Pre and Post-dose Plasma Vemurafenib Concentration by Study Day

Time: Plasma samples were collected before the morning dose (troughs) and 2-4 hours after the morning dose at the beginning of each cycle (Days 1, 22, 43, 64, 106, 148 and 190).

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine. --- V600E ---

The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.. Inclusion Criteria: - adults, >/=18 years of age - metastatic melanoma, stage IIIC or IV (AJCC) - treatment-naïve (no prior systemic anticancer therapy) - positive for BRAF V600E mutation - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active central nervous system metastases - history of carcinomatous meningitis - severe cardiovascular disease within 6 months prior to study drug administration - previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix Inclusion Criteria: - adults, >/=18 years of age - metastatic melanoma, stage IIIC or IV (AJCC) - treatment-naïve (no prior systemic anticancer therapy) - positive for BRAF V600E mutation - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active central nervous system metastases - history of carcinomatous meningitis - severe cardiovascular disease within 6 months prior to study drug administration - previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix Malignant Melanoma Melanoma null --- V600E ---

The pharmacokinetics of vemurafenib were assessed at the beginning of each 21-day cycle using pre-dose and 2-4 hours post-dose sampling.. Inclusion Criteria: - adults, >/=18 years of age - metastatic melanoma, stage IIIC or IV (AJCC) - treatment-naïve (no prior systemic anticancer therapy) - positive for BRAF V600E mutation - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active central nervous system metastases - history of carcinomatous meningitis - severe cardiovascular disease within 6 months prior to study drug administration - previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix Inclusion Criteria: - adults, >/=18 years of age - metastatic melanoma, stage IIIC or IV (AJCC) - treatment-naïve (no prior systemic anticancer therapy) - positive for BRAF V600E mutation - measurable disease by RECIST criteria - negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion Exclusion Criteria: - active central nervous system metastases - history of carcinomatous meningitis - severe cardiovascular disease within 6 months prior to study drug administration - previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix Malignant Melanoma Melanoma null --- V600E --- --- V600E ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 15
HRAS MITF CDKN2A BRAF NRAS NRAS WRN CDKN2A CXCR4 BAP1 POLH CDK4 ERCC3 XPC MC1R
Melanoma
Genes 98
MGMT NRAS POT1 NRAS XPA CTSC BRCA1 SDHC ERCC4 CXCR4 RAD51C CDKN2B ERCC3 XPC PALLD ERCC2 ERCC2 CHEK2 CDKN2A RAD51D GNAQ SDHD KRAS MBTPS2 BAP1 BAP1 CYSLTR2 RNF43 BAP1 CDKN2A PTPN11 CDK4 BRCA2 ERCC3 MITF TERF2IP ERCC4 CHEK2 BRCA1 TRPV3 POT1 OCA2 TERT CDKN2A AKT1 CDKN2A SF3B1 ERCC6 ERCC5 ERCC5 MDM2 BRCA2 BAP1 GNA11 ACD BRIP1 HRAS MRE11 BRAF TYR TP53 KLLN SEC23B PTEN PIK3CA XPA PERP MITF RAF1 BRAF POLH TP53 BARD1 NRAS SMAD4 RAD50 DDB2 ERCC2 NBN TERT MC1R SLC45A2 WRN PALB2 DDB2 PALB2 CDKN2A SDHB MC1R RAD51 TP53 XPC ERCC3 PTEN CDKN2A POLH CDK4 MC1R