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Phase 3 N=704 Randomized Treatment

Dabrafenib Plus Trametinib vs Vemurafenib Alone in Unresectable or Metastatic BRAF V600E/K Cutaneous Melanoma

Melanoma

Enrolled (actual)
704
Serious AEs
45.0%
Results posted
Dec 2014
Primary outcome: Primary: Overall Survival (OS) — 26.0; 17.8 Months

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Dabrafenib (Drug); Vemurafenib (Drug); Trametinib (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Novartis Pharmaceuticals
Primary completion
Apr 2014

Outcome Measures

OutcomeResultp-value
PRIMARY
Overall Survival (OS)
26.0; 17.8
SECONDARY
Progression-Free Survival (PFS), as Assessed by the Investigator
12.1; 7.3
SECONDARY
Overall Response Rate (ORR) During Randomized Phase, as Assessed by the Investigator
68; 53
SECONDARY
Duration of Response (DOR), as Assessed by the Investigator
13.8; 8.5

Summary

This was a two-arm, open-label, randomized, Phase III study comparing dabrafenib (GSK2118436) and trametinib (GSK1120212) combination therapy with vemurafenib.

Eligibility Criteria

Key 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

Key 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 = 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)
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01597908). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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