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Report for Clinical Trial NCT01597908

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma

This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible although prior systemic treatment in the adjuvant setting will be allowed. Approximately 694 subjects will be randomised 1:1 (combination therapy:vemurafenib). The primary endpoint is overall survival (OS) for subjects receiving the combination therapy compared with those receiving vemurafenib.

NCT01597908 Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

3 Interventions

Name: Dabrafenib

Description: dabrafenib 150 mg twice daily po

Type: Drug

Dabrafenib plus Trametinib

Name: Vemurafenib

Description: vemurafenib 960 mg twice daily po

Type: Drug

Vemurafenib

Name: Trametinib

Description: trametinib 2 mg once daily po

Type: Drug

Dabrafenib plus Trametinib


Primary Outcomes

Description: Overall survival is defined as the time from randomization until death due to any cause.

Measure: Overall Survival

Time: From randomization until death due to any cause (up to Study Week 92)

Secondary Outcomes

Description: Progression-free survival (PFS) is defined as the time from randomization to the first documented occurrence of disease progression or death due to any cause. PFS for investigator-assessed response was summarized per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, which is a set of published rules defining when cancer patients improve (respond), stay the same (stabilize), or worsen (progress) during treatment. Disease progression is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation.

Measure: Progression-free Survival, as Assessed by the Investigator

Time: From randomization to the first documented occurrence of disease progression or death due to any cause (up to Study Week 80)

Description: Overall response is defined as the number of responders (complete response [CR] + partial response [PR] per RECIST, Version 1.1) as summarized by Investigator assessment. CR is defined as the disappearance of all evidence of target lesions. PR is defined as at least a 30% reduction from Baseline in the sum of the longest diameter (LD) of all target lesions. Data are reported as those participants with measureable disease.

Measure: Overall Response, as Assessed by the Investigator

Time: Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks

Description: Duration of response is defined as the time from the first documented evidence of a CR (disappearance of all evidence of target lesions) or a PR (at least a 30% reduction from Baseline in the sum of the longest diameter of all target lesions) until disease progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5 mm or the appearance of at least1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. Data are summarized per RECIST, Version 1.1.

Measure: Duration of Response, as Assessed by the Investigator

Time: From the first documented evidence of a CR or PR until the earliest date of disease progression or death due to any cause (up to Study Week 80)

Purpose: Treatment

Allocation: Randomized


There is one SNP

SNPs


1 V600E

A Phase III, Randomised, Open-label Study Comparing the Combination of the BRAF Inhibitor, Dabrafenib and the MEK Inhibitor, Trametinib to the BRAF Inhibitor Vemurafenib in Subjects With Unresectable (Stage IIIc) or Metastatic (Stage IV) BRAF V600E/K Mutation Positive Cutaneous Melanoma. --- V600E ---

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma This is a two-arm, open-label, randomised, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy to vemurafenib. --- V600E ---

Subjects with histologically confirmed cutaneous melanoma that is either stage IIIc (unresectable) or stage IV, and BRAF V600E/K mutation positive will be screened for eligibility. --- V600E ---

Data are summarized per RECIST, Version 1.1.. Inclusion Criteria: - >= 18 years of age - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function Exclusion Criteria: - Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) Inclusion Criteria: - >= 18 years of age - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function Exclusion Criteria: - Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) Melanoma Melanoma null --- V600E ---

Data are summarized per RECIST, Version 1.1.. Inclusion Criteria: - >= 18 years of age - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function Exclusion Criteria: - Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) Inclusion Criteria: - >= 18 years of age - Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma - Measurable disease according to RECIST 1.1 - Women of childbearing potential with negative serum pregnancy test prior to randomisation - Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 - Adequate baseline organ function Exclusion Criteria: - Any prior use of a BRAF or MEK inhibitor - Prior systemic anti-cancer treatment in the advanced or metastatic setting; prior systemic treatment in the adjuvant setting is allowed - History of another malignancy (except subjects who have been disease free for 3 years or with a history of completely resected non-melanoma skin cancer) - Known HIV, HBV, HCV infection (except chronic or cleared HBV and HCV infection which will be allowed) - Brain metastases (except if all known lesions were previously treated with surgery or stereotactic radiosurgery and lesions, if still present, are confirmed stable for >= 12 weeks prior to randomisation or if no longer present are confirmed no evidence of disease for >= 12 weeks, and are asymptomatic with no corticosteroid requirements for >= 4 weeks prior to randomisation, and no enzyme inducing anticonvulsants for >= 4 weeks prior to randomisation - History or evidence of cardiovascular risk (LVEF < LLN; QTcB >= 480 msec; blood pressure or systolic >=140 mmHg or diastolic >= 90 mmHg which cannot be controlled by anti-hypertensive therapy) - History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) 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