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

May 10, 2012
December 4, 2014
June 2012
September 2018   (final data collection date for primary outcome measure)
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.
Overall Survival [ Time Frame: approx. 20 months ] [ Designated as safety issue: No ]
time from randomisation until death due to any cause
Complete list of historical versions of study NCT01597908 on ClinicalTrials.gov Archive Site
  • 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.
  • 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)
Not Provided
Not Provided
 
Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Melanoma
  • Drug: Dabrafenib
    dabrafenib 150 mg twice daily po
  • Drug: Vemurafenib
    vemurafenib 960 mg twice daily po
  • Drug: Trametinib
    trametinib 2 mg once daily po
  • Experimental: Dabrafenib plus Trametinib
    BRAF inhibitor plus MEK inhibitor
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
  • Active Comparator: Vemurafenib
    BRAF inhibitor
    Intervention: Drug: Vemurafenib
Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin AM, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015 Jan 1;372(1):30-9. doi: 10.1056/NEJMoa1412690. Epub 2014 Nov 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
704
September 2018
September 2018   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Czech Republic,   Denmark,   Finland,   France,   Germany,   Hungary,   Ireland,   Israel,   Italy,   Korea, Republic of,   Netherlands,   New Zealand,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   Taiwan,   Ukraine,   United Kingdom
 
NCT01597908
116513
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP