A study to test two investigational drugs, dabrafenib and trametinib, for treating melanoma

Phase 1

Active, not recruiting

• Conditions: Cutaneous melanoma - aggressive form of skin cancers.; MedDRA version: 14.1Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-006087-49-IT
• Lead Sponsor: GLAXOSMITHKLINE RESEARCH & DEVELOPMENT LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-04-24
• Study Completion: 2019-02-28
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 423

Inclusion Criteria

Subjects eligible for enrolment in the study must meet all of the following criteria: 1. = 18 years of age. 2. Signed written informed consent. 3. Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastic), and determined to be BRAF V600E/K mutationpositive using the bioMerieux (bMx) investigational use only (IUO) THxID BRAF Assay (IDE: G120011). The assay will be conducted by a central reference laboratory. Subjects with ocular or mucosal melanoma are not eligible. XML File Identifier: rSVgypuV11yA3U5AvZ/g44SU77Y= Page 23/37 4. Measurable disease (i.e., present with at least one measurable lesion per RECIST, version 1.1. Refer to Section 7.2.3.1 of protocol for the definition of a measureable lesion. 5. All prior anti-cancer treatment-related toxicities (except alopecia) must be = Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 at the time of randomization. 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. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to randomization and agree to use effective contraception, as defined in Section 7.3.3 of protocol, throughout the treatment period, and for 30 days after the last dose of study treatment. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in Section 7.3.3 of protocol from 14 days prior to randomization, throughout the treatment period, and for 16 weeks after the last dose of study treatment. 8. An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 9. Adequate baseline organ function as defined in Table 2 (page 25 of Protocol). 10. Subjects enrolled in France: 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: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 265
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1.Prior treatment with a BRAF inhibitor or a MEK inhibitor 2. Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. (Ipilimumab treatment must end at least 8 weeks prior to randomization.)3. Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to randomization and/or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to randomization. 4. Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to randomization 5. prohibited medication 6. History of another malignancy. Exception: Subjects who have been disease-free for 3 years, or subjects with a history of completely resected non-melanoma skin cancer, and/or subjects with indolent second malignancies are eligible 7.Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.8. 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 will be allowed)9. A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency.10. Brain metastasis are excluded unless: a. All known lesions were previously treated with surgery or stereotactic surgery (whole-brain radiation is not allowed unless given after definitive treatment with surgery or stereotactic surgery), AND b. Brain lesion(s), if still present, must be confirmed stable (i.e., no increase in lesion size) for = 12 weeks prior to randomization (stability must be confirmed with two consecutive magnetic resonance image (MRI) or computed tomography (CT) scans with contrast, AND c. Asymptomatic with no corticosteroid requirements for = 4 weeks prior to randomization, AND d. No enzyme inducing anticonvulsants for = 4 weeks prior to randomization In addition, for subjects that had brain metastases but currently have no evidence of disease (NED), NED for =12 weeks is required and must be confirmed by two consecutive scans, separated by =6 weeks, prior to randomization 11. A history or evidence of cardiovascular risk (see the protocol)12.A history or current evidence/risk of retinal vein occlusion (RVO) or 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 mmHg as measured by tonography. 13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).14. Females who are nursing.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified