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

Trial Status: Complete

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

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)

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: CLOSED_TO_ACCRUAL

Colorado

Aurora
University of Colorado Hospital
Status: COMPLETED
Contact: Karl D. Lewis

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: COMPLETED

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: COMPLETED

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: COMPLETED

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: COMPLETED
Durham
Duke University Medical Center
Status: COMPLETED

Oregon

Portland
OHSU Knight Cancer Institute
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION

South Carolina

Charleston
Medical University of South Carolina
Status: COMPLETED

Tennessee

Nashville
Vanderbilt University / Ingram Cancer Center
Status: COMPLETED

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: COMPLETED

Virginia

Charlottesville
University of Virginia Cancer Center
Status: COMPLETED

Screening/Subject eligibility: Subjects with histologically confirmed cutaneous melanoma that

was either unresectable or metastatic (Stages IIIC or IV), were screened for eligibility.

Eligible subjects were BRAF V600E or V600K mutation positive. Subjects who had prior systemic

anti-cancer treatment in the advanced or metastatic setting were not eligible although prior

systemic treatment in the adjuvant setting was allowed.

Randomization: A total of 704 subjects were randomized in a ratio of 1:1 to receive

combination therapy (352 subjects) or vemurafenib treatment (352 subjects). Subjects were

stratified by LDH level (> the ULN versus =< ULN) and BRAF mutation (V600E versus V600K).

Study treatment: Dabrafenib and trametinib were administered orally at their recommended

doses of 150 mg b.i.d. and 2.0 mg once daily, respectively. Subjects randomized in the

combination therapy arm received both the agents. Subjects randomized in the vemurafenib arm

received vemurafenib at the recommended dose of 960 mg orally b.i.d. Subjects in both the

arms continued treatment until disease progression, death, unacceptable toxicity, or

withdrawal of consent. The protocol was amended on 07-Aug-2014 which allowed subjects who

were still receiving vemurafenib to cross over to the dabrafenib and trametinib combination

arm, including those subjects who were still receiving vemurafenib monotherapy treatment

after disease progression. A washout period of a minimum of 7 days was considered prior to

initiating dabrafenib in combination with trametinib. Subjects who experienced disease

progression on the vemurafenib monotherapy arm, discontinued vemurafenib monotherapy, and

subsequently received another anticancer therapy were ineligible for cross over to the

dabrafenib and trametinib combination arm.

Follow-up/Study closure: After study treatment discontinuation, subjects were followed for

survival and disease progression as applicable. This study completed once all the subjects

had at least the 5-years of follow-up.

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID 116513
  • Secondary IDs NCI-2012-01414, 2011-006088-23, CDRB436B2302
  • Clinicaltrials.gov ID NCT01597908