BRAF mutation positive metastatic melanoma MedDRA version: 12.1 Level: LLT Classification code 10025670 Term: Malignant melanoma stage III MedDRA version: 12.1 Level: LLT Classification code 10025671 Term: Malignant melanoma stage IV
Conditions
Interventions
Product Name: GSK2118436
Product Code: GSK2118436
Pharmaceutical Form: Capsule*
CAS Number: 1195768-06-9
Current Sponsor code: GSK2118436
Other descriptive name: GSK2118436B
Concentration unit: mg mil
Sponsors
GlaxoSmithKline
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Has provided signed informed consent. 2. Histologically confirmed advanced (unresectable Stage III) or metastatic melanoma (Stage IV) and BRAF mutation-positive (V600 E) melanoma as determined via central testing with a BRAF mutation assay. 3. Are treatment naïve for advanced (unresectable) or metastatic melanoma, with the exception of IL-2 which is allowed. 4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 5. Age =18 years of age 6. Able to swallow and retain oral medication. 7. Women with child-bearing potential and men with reproductive potential must be willing to practice acceptable methods of birth control during the study. Additionally, women of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 9. Must have adequate organ function as defined in the protocol (Retesting of borderline screening organ function will be allowed. Treatment with transfusion, growth factors to meet eligibility criteria will not be allowed): 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Previous treatment for metastatic melanoma, including treatment with BRAF or MEK inhibitor. 2. Known ocular or primary mucosal melanoma. 3. Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, or surgery). 4. Use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of GSK2118436. 5. Current use of a prohibited medication or is expected to require any of these medications during treatment with GSK2118436. 6. Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks. 7. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GSK medical monitor for permission to enroll the subject. 8. A history of Human Immunodeficiency Virus (HIV) infection 9. A history of glucose-6-phosphate dehydrogenase (G6PD) deficiency. 10. A history of other malignancy. 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 11. Evidence of active CNS disease (radiographically unstable, symptomatic lesions). However prior treatment with stereotactic radiosurgery (SRS) or surgical resection is allowed if the subject remains without evidence of disease progression in the brain = 3 months, and has been off corticosteroids = 3 weeks. Whole brain radiotherapy is not allowed except in those subjects who have had definitive resection or SRS of all radiographically detectable parenchymal lesions. 12. History of alcohol or drug abuse within 6 months prior to Screening. 13. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, or unwillingness or inability to follow the procedures required in the protocol. 14. The following cardiac abnormalities: • Corrected QT (QTc) interval = 480 msecs • History of acute coronary syndromes (including unstable angina) within the past 24 weeks. • Coronary angioplasty, or stenting within the past 24 weeks. • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system • Abnormal cardiac valve morphology (= grade 2) documented by echocardiogram (subjects with grade 1 abnormalities [ie, mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study. • History of known cardiac arrhythmias (except sinus arrhythmia) within the past 24 weeks. • Known cardiac metastases. 15. Pregnant or lactating female.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective for this study is to establish the superiority of GSK2118436 over DTIC with respect to progression-free survival for subjects with BRAF mutation positive metastatic melanoma;Secondary Objective: The secondary objectives for this study are to compare overall survival and best overall response between treatment groups, to describe progression-free survival of subjects in the DTIC treatment group after initial progression and subsequent cross-over to GSK2118436, to describe duration of response in subjects receiving GSK2118436, to assess the rate of non-melanoma skin lesions and second malignancies in both treatment groups, to further validate a BRAF mutation assay, to compare between treatment arms the change in quality of life (QoL) relative to baseline using the EORTC-QLQ-C30, to assess the change in QoL relative to baseline using the EORTC-QLQ-C30 in subjects in the DTIC treatment group after initial progression and subsequent cross-over to GSK2118436, to further characterize the safety, and tolerability of GSK2118436 administered as a single agent, and to evaluate the qualitative and quantitative toxicities between treatment arms. ;Primary end point(s): The primary efficacy endpoint of this study is progression free survival (PFS). For this study, PFS is defined as the time from randomization until the first date of either objective disease progression or death due to any cause. | — |
Countries
Germany, Hungary, Ireland, Italy, Netherlands, Spain
Outcome results
None listed