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Report for Clinical Trial NCT01153763

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase II (BRF113710) Single-arm, Open-label Study of GSK2118436 in BRAF Mutant Metastatic Melanoma

BRF113710 is a Phase II, single-arm, open-label study to assess the efficacy, safety, and tolerability of GSK2118436 administered twice daily as a single agent in subjects with BRAF mutant metastatic melanoma. Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.

NCT01153763 Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

1 Interventions

Name: GSK2118436

Description: Subjects will receive 150 mg of GSK2118436 twice daily and continue on treatment until disease progression, death, or unacceptable adverse event.

Type: Drug

All patients


Primary Outcomes

Description: A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeter (mm) in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment was required at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later were required to be confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Primary efficacy Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600E mutation.

Measure: Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation

Time: Up to 60 months

Secondary Outcomes

Description: A participant was defined as a responder if he/she achieved either a CR (the disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis.) or PR (at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters [e.g., percent change from Baseline]). To be assigned a status of PR or CR, a confirmatory disease assessment had to have been performed at Week 12 if an initial response was seen at the Week 6 scan. Initial responses (CR/PR) that occured at Week 12 or later should have been confirmed not less than 4 weeks and not more than 6 weeks after the criteria for response were first met. The analysis was performed on Secondary efficacy analysis Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600K mutation.

Measure: Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation

Time: Up to 60 months

Description: PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent confidence interval (CI). For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.

Measure: Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation

Time: Up to 60 months

Description: PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or progression minus date of first dose plus 1 day. Kaplan-Meier model was used to estimate the median and 95 percent CI. For participants who received subsequent anti-cancer therapy prior to the date of documented progression or death, PFS was censored at the last adequate assessment. For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.

Measure: Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation

Time: Up to 60 months

Description: Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Primary efficacy Population and only those participants who had a CR or PR were analyzed.

Measure: Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation

Time: Up to 60 months

Description: Duration of response for participants with either a CR or PR is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. Duration of response was estimated using Kaplan-Meier model and the median and 95 percent CI was presented. The analysis was performed on Secondary efficacy Population and only those participants who had a CR or PR were analyzed.

Measure: Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation

Time: Up to 60 months

Description: Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using kaplan-Meier model and median and 95 percent CI was presented.

Measure: Overall Survival for Participants Who Had a BRAF V600E Mutation

Time: Up to 60 months

Description: Overall survival is defined as the time from the first dose of study medication until death due to any cause. For participants who did not die, overall survival was censored at the date of last contact. Overall survival was estimated using Kaplan-Meier model and median and 95 percent CI was presented.

Measure: Overall Survival for Participants Who Had a BRAF V600K Mutation

Time: From the first dose to death due to any cause (up to 60 months)

Description: An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs including systemic allergic and non-allergic reactions as well as local site injection-related reactions were counted throughout treatment phase and follow up phase. Systemic allergic reactions included facial paralysis, flushing, hypersensitivity and rash pruritic. Injection related reactions were considered as systemic non-allergic reactions. Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on All treated Population which comprised of all participants that receive at least one dose of dabrafenib.

Measure: Number of Participants With AEs and Serious Adverse Events (SAEs)

Time: Up to 60 months

Description: Blood samples were collected from participants for evaluation of change from Baseline in toxicity grades in clinical chemistry and hematology parameters. The clinical chemistry parameters included alkaline phosphatase, Alanine amino transferase (ALT), Aspartate amino transferase (AST), total bilirubin, creatinine, glucose, potassium, magnesium, sodium and phosphorus. The hematology parameters included hemoglobin, total neutrophils, platelets and white blood cells (WBC). Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Measure: Number of Participants With Change From Baseline in Clinical Chemistry and Hematology Toxicity Grades

Time: Up to 60 months

Description: Number of participants with change from Baseline in temperature and pulse rate were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as decrease to <=35, change to normal or no change and increase to >=38. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst case post-baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.

Measure: Number of Participants With Change From Baseline in Temperature and Pulse Rate

Time: Up to 60 months

Description: Number of participants with increase from Baseline in SBP and DBP were evaluated from the first dose of study treatment till discontinuation due to any reason. Change from Baseline in worst-case post Baseline value was presented as any increase to >=80 and increase to >=100 for DBP and as any increase to >=120 and increase to >=160 for SBP. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period. One participant out of the 92 participants (76 BRAF V600E patients + 16 BRAF V600K patients) did not have SBP and DBP collected after baseline.

Measure: Number of Participants With Increase From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Time: Up to 60 months

Description: LVEF was defined as the percentage of blood pumped out of the left ventricle. Change from Baseline in worst-case post Baseline was presented as no change or any increase and any decrease values. Baseline was defined as the most recent non-missing value prior to the first dose of study treatment. The change from Baseline was calculated as visit value minus Baseline value and was presented in the form of worst-case post Baseline value which was the maximum toxicity grade for a participant after the first dose of study drug over the treatment period.

Measure: Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels

Time: Up to 60 months

Purpose: Treatment

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

Number of Participants With a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator for Participants Who Had a BRAF V600E Mutation. --- V600E ---

The analysis was performed on Primary efficacy Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600E mutation.. Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation. --- V600E ---

The analysis was performed on Secondary efficacy analysis Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600K mutation.. Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation. --- V600K --- --- V600E ---

For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.. Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation. --- V600E ---

The analysis was performed on Secondary efficacy Population and only those participants who had a CR or PR were analyzed.. Overall Survival for Participants Who Had a BRAF V600E Mutation. --- V600E ---

One participant out of the 92 participants (76 BRAF V600E patients + 16 BRAF V600K patients) did not have SBP and DBP collected after baseline.. Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels. --- V600E ---


2 V600K

The analysis was performed on Primary efficacy Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600E mutation.. Number of Participants With a Best Overall Response of CR or PR as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation. --- V600E --- --- V600K ---

The analysis was performed on Secondary efficacy analysis Population which comprised of all participants who received at least one dose of GSK2118436 (All Treated Participants Population) and had a BRAF V600K mutation.. Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600E Mutation. --- V600K ---

For participants who did not have a documented date of progression or death, PFS was censored at the date of last adequate assessment.. Progression-free Survival (PFS) as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation. --- V600K ---

The analysis was performed on Primary efficacy Population and only those participants who had a CR or PR were analyzed.. Duration of Response as Assessed by the Investigator and an Independent Reviewer for Participants Who Had a BRAF V600K Mutation. --- V600K ---

Overall survival was estimated using kaplan-Meier model and median and 95 percent CI was presented.. Overall Survival for Participants Who Had a BRAF V600K Mutation. --- V600K ---

One participant out of the 92 participants (76 BRAF V600E patients + 16 BRAF V600K patients) did not have SBP and DBP collected after baseline.. Number of Participants With Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Levels. --- V600E --- --- V600K ---



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