Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma (COMBI-v)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01597908
First received: May 10, 2012
Last updated: December 4, 2014
Last verified: December 2014
  Purpose

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.


Condition Intervention Phase
Melanoma
Drug: Dabrafenib
Drug: Vemurafenib
Drug: Trametinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Overall Survival [ Time Frame: From randomization until death due to any cause (up to Study Week 92) ] [ Designated as safety issue: No ]
    Overall survival is defined as the time from randomization until death due to any cause.


Secondary Outcome Measures:
  • Progression-free Survival, as Assessed by the Investigator [ Time Frame: From randomization to the first documented occurrence of disease progression or death due to any cause (up to Study Week 80) ] [ Designated as safety issue: No ]
    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.

  • Overall Response, as Assessed by the Investigator [ Time Frame: Screening, Week 8 and every 8 weeks thereafter through Week 56, and then every 12 weeks ] [ Designated as safety issue: No ]
    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.

  • Duration of Response, as Assessed by the Investigator [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 704
Study Start Date: June 2012
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dabrafenib plus Trametinib
BRAF inhibitor plus MEK inhibitor
Drug: Dabrafenib
dabrafenib 150 mg twice daily po
Drug: Trametinib
trametinib 2 mg once daily po
Active Comparator: Vemurafenib
BRAF inhibitor
Drug: Vemurafenib
vemurafenib 960 mg twice daily po

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597908

  Show 205 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01597908     History of Changes
Other Study ID Numbers: 116513
Study First Received: May 10, 2012
Results First Received: December 1, 2014
Last Updated: December 4, 2014
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
MEK inhibitor
Metastatic Melanoma
BRAF inhibitor
Cancer

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas
Dabrafenib
Trametinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on May 26, 2015