A study of the BRAF inhibitor dabrafenib in combination with the MEK inhibitor trametinib compared to two placebos (inactive drugs) in the treatment of BRAF V600E/K mutation-positive melanoma after surgery.
- Conditions
- High-risk BRAF V600 mutation-positive melanoma after surgical resection.MedDRA version: 20.0Level: HLTClassification code 10027156Term: Skin melanomas (excl ocular)System Organ Class: 100000004858Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001266-15-GR
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 852
1. Is 18 years of age or older
2. Has signed written informed consent.
3. Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis>1 mm), IIIb or IIIc; for Staging Guidelines] cutaneous
melanoma determined to be V600E/K mutation positive using the bioMerieux (bMX) THxID BRAF Assay. The testing will be conducted by a central reference laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. Patients with an unknown primary melanoma are not eligible.
4. Must be surgically rendered free of disease (defined as the date of the most recent surgery) no more than 12 weeks before randomization.
5. Recovered from definitive surgery (e.g. no uncontrolled wound infections or indwelling drains).
6. Able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 [Oken, 1982].
8. Must have adequate organ function.
9. Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in Section 7.3.3 from 14 days prior to randomization, throughout the treatment period and for 4 months after the last dose of study treatment.
10. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 852
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
2. Evidence of distant metastatic disease on screening evaluation.
3. Prior anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) including radiotherapy for melanoma. Prior surgery for melanoma is allowed.
4. Taken an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to randomization.
5. Current or expected use of a prohibited medication (See Protocol Section 6.2 for a list prohibited medications).
6. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
7. Known Human Immunodeficiency Virus (HIV).
8. History of another malignancy including melanoma or a concurrent malignancy except as noted below. Patients who have previously had Stage III melanoma or any malignancy with confirmed activating RAS mutation at any time are not eligible.
Note: Prospective RAS testing is not required. However, if the results of previous RAS testing are known, they must be used in assessing eligibility.
Exceptions:
- Patients with a history of any malignancy that have been disease-free for at least 5 years are eligible except those with confirmed activating RAS mutations.
- Patients with a history of completely resected non-melanoma skin cancer (e.g. basal cell carcinoma, squamous cell carcinoma) are eligible irrespective of the time since the resection.
- Patients with successfully treated in situ carcinoma are eligible.
- Patients presenting with multiple primary melanomas are eligible only if the lesions are concurrent. Patients who have concurrent multiple primary melanomas that are distant” are eligible provided each lesion is considered local disease or resectable regional disease. These cases should be discussed with the Medical Monitor.
9. A history or evidence of cardiovascular risk including any of the following:
a. A QT interval corrected for heart rate using the Bazett’s formula (QTcB) >480 msec;
b. A history or evidence of current clinically significant uncontrolled
arrhythmias;
c. A history of acute coronary syndromes (including myocardial infarction or unstable angina), coronary angioplasty, or stenting within 6 months prior to randomization
d. A history or evidence of current > Class II congestive heart failure as
defined by the New York Heart Association (NYHA) guidelines
e. Patients with intra-cardiac defibrillators.
f. Abnormal cardiac valve morphology (=grade 2) documented by
echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study.
g. Treatment refractory hypertension defined as a blood pressure of
systolic> 140 mm Hg and/or diastolic > 90 mm Hg which cannot be
controlled by anti-hypertensive therapy.
10. A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:
a. Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or
b. Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as:
i. Evidence of new optic disc cupping;
ii
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method