SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01006980

Developed by Shray Alag, 2019.
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 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