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: March 27, 2014
Last verified: March 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: approx. 20 months ] [ Designated as safety issue: No ]
    time from randomisation until death due to any cause


Secondary Outcome Measures:
  • Progression Free Survival [ Time Frame: approx. 10 months ] [ Designated as safety issue: No ]
    time from randomisation to until the earliest date of disease progression or death due to any cause

  • Overall Response Rate [ Time Frame: approx. 10 months ] [ Designated as safety issue: No ]
    percentage of subjects with a confirmed or unconfirmed completed response (CR) or partial response (PR) at any time per RECIST 1.1

  • Duration of Response [ Time Frame: approx. 10 months ] [ Designated as safety issue: No ]
    time from first documented evidence of CR or PR until disease progression or death due to any cause among subjects who achieve an overall response (i.e., confirmed or unconfirmed CR or PR)


Enrollment: 694
Study Start Date: June 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2014 (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
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

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01597908     History of Changes
Other Study ID Numbers: 116513
Study First Received: May 10, 2012
Last Updated: March 27, 2014
Health Authority: Australia: Human Research Ethics Committee
United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Melanoma
Skin Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on April 17, 2014