A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection. (COMBI-AD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01682083
First received: September 6, 2012
Last updated: August 14, 2014
Last verified: August 2014

September 6, 2012
August 14, 2014
January 2013
July 2015   (final data collection date for primary outcome measure)
Relapse-free survival (RFS) [ Time Frame: Approximately 32 months ] [ Designated as safety issue: No ]
Relapse-free survival (RFS) in subjects [ Time Frame: From date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed for an average of 24 months ] [ Designated as safety issue: No ]
The efficacy of dabrafenib and trametinib combination therapy compared to placebo was evaluated by measuring RFS. Relapse Free Survival is defined as the time from randomization to disease recurrence or death from any cause. Recurrence of or death from the same cancer and all deaths from other causes are events. Treatment emergent malignancy(ies) other than second melanomas will not be considered as events, and loss to follow-up is censored. Subjects without RFS events will be censored at the last assessment
Complete list of historical versions of study NCT01682083 on ClinicalTrials.gov Archive Site
  • Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
  • Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: approximately 32 months ] [ Designated as safety issue: No ]
  • Safety of dabrafenib and trametinib as a combination therapy in the overall study population [ Time Frame: approximately 5 years ] [ Designated as safety issue: No ]
  • Overall survival (OS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: From date of randomization until the date of death, assessed for an average of 24 months ] [ Designated as safety issue: No ]
    OS is defined as the interval from randomization to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact
  • Distant metastasis-free survival (DMFS) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: From date of randomization until the date of first documented distant metastasis or date of death, whichever came first, assessed for an average of 24 months ] [ Designated as safety issue: No ]
    DMFS is defined as the interval from randomization to the date of first distant metastasis or date of death, whichever occurs first. Subjects alive and without distant metastasis are censored at the date of last assessment
  • Freedom from relapse (FFR) of dabrafenib and trametinib as a combination therapy versus placebo [ Time Frame: From date of randomization until the date of first documented local or distant recurrence, assessed for an average of 24 months ] [ Designated as safety issue: No ]
    FFR is defined as interval from randomization to local or distant recurrence with censoring of subjects dying from causes other than melanoma or treatment-related toxicity at the date of death. Subjects alive without recurrence or with second primary cancers will be censored at the date of last assessment
  • Safety of dabrafenib and trametinib as a combination therapy in the overall study population [ Time Frame: Duration of the study (upto 24 months) ] [ Designated as safety issue: No ]
    Safety will be measured by clinical assessments including vital signs and physical examinations, 12-lead electrocardiograms (ECG), echocardiogram (ECHO), eye exams, chemistry and hematology laboratory values, and adverse events (AEs)
Not Provided
Not Provided
 
A Study of the BRAF Inhibitor Dabrafenib in Combination With the MEK Inhibitor Trametinib in the Adjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection.
COMBI-AD: A Phase III Randomized Double Blind Study of Dabrafenib (GSK2118436) in COMBInation With Trametinib (GSK1120212) Versus Two Placebos in the ADjuvant Treatment of High-risk BRAF V600 Mutation-positive Melanoma After Surgical Resection

This is a two-arm, randomized, double-blind Phase III study of dabrafenib in combination with trametinib versus two placebos in the adjuvant treatment of melanoma after surgical resection. Patients with completely resected, histologically confirmed, BRAF V600E/K mutation-positive, high-risk [Stage IIIa (lymph node metastasis >1 mm), IIIb or IIIc] cutaneous melanoma will be screened for eligibility. Subjects will be randomized to receive either dabrafenib (150 milligram (mg) twice daily [BID]) and trametinib (2 mg once daily [QD]) combination therapy or two placebos for 12 months.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Melanoma
  • Drug: Dabrafenib
    Each capsule contains 50 mg or 75 mg of free base (present as the mesylate salt)
  • Drug: Trametinib
    Each tablet contains 0.5 mg or 2.0 mg of trametinib parent (present as the DMSO solvate)
  • Drug: Placebos
    The placebo capsules and tablets contain the same inactive ingredients and film coatings as the dabrafenib and trametinib study treatment
  • Experimental: Dabrafenib and trametinib combination therapy
    Subjects will receive dabrafenib (150 mg twice daily) and trametinib (2 mg once daily) orally for 12 months.
    Interventions:
    • Drug: Dabrafenib
    • Drug: Trametinib
  • Placebo Comparator: Dabrafenib and trametinib placebos
    Subjects will receive matching placebos orally for 12 months
    Intervention: Drug: Placebos
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
852
July 2015
July 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
  • Surgically rendered free of disease no more than 12 weeks before randomization.
  • Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  • Adequate hematologic, hepatic, renal and cardiac function.

Exclusion Criteria:

  • Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
  • Evidence of distant metastatic disease.
  • Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
  • History of another malignancy or concurrent malignancy including prior malignant melanoma. Exceptions to this include: Patients who have been disease-free for 5 years or patients with a history completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible, for example cervical cancer in situ, atypical melanocytic hyperplasia or melanoma in situ, multiple primary melanomas, or other malignancies for which the patient has been disease free for > 5 years.
  • History or current evidence of cardiovascular risk.
  • History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Both
18 Years and older
No
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
United States,   Argentina,   Australia,   Austria,   Belgium,   Canada,   Czech Republic,   Denmark,   France,   Germany,   Greece,   Israel,   Italy,   Japan,   Netherlands,   New Zealand,   Norway,   Poland,   Russian Federation,   Spain,   Sweden,   Switzerland,   Taiwan,   United Kingdom
 
NCT01682083
115532
Yes
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
August 2014

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