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: 15.1Level: HLTClassification code 10027156Term: Skin melanomas (excl ocular)System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2012-001266-15-ES
- Lead Sponsor
- GlaxoSmithKline, S.A.
- 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; cutaneous melanoma determined to be V600E/K mutation positive using the bioMerieux (bMX) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible.
4.Must be surgically rendered free of disease 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 682
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 170
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 systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) and 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
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), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which are allowed).
8. A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
9. History of another malignancy or a concurrent malignancy including prior malignant melanoma except as noted below;
Exception: Subjects who have been disease-free for 5 years, or subjects with a history of 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 except those known to have had a KRAS mutation.
10. 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; Appendix 5) >= 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 or permanent pacemakers;
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 HgmmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapy.
11. 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. Evidence of new visual field defects on automated perimetry;
iii. Intraocular pressure >21 mm mmHg as measured by tonography.
13. Interstitial lung disease or pneumonitis.
14. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that, in the opinion of the investigator, could int
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