A Phase II (BRF113710) single-arm, open-label study of dabrafenib (GSK2118436) in BRAF mutant metastatic melanoma
- Conditions
- BRAF Mutant Metastatic MelanomaMedDRA version: 18.1Level: LLTClassification code 10027481Term: Metastatic melanomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2009-015297-36-DE
- Lead Sponsor
- GlaxoSmithKline, Research and Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
Specific information regarding warnings, precautions, contraindications, adverse events, and other pertinent information on the study treatment that may impact subject eligibility is provided in the IB [GlaxoSmithKline Document Number CM2010/00010/03].
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Has signed informed consent.
2. Histologically confirmed metastatic melanoma (Stage IV), with BRAF mutation-positive (V600 E/K) melanoma as determined via central testing with a BRAF mutation assay.
3. Is treatment naïve or has received prior treatment for metastatic melanoma
4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) [Eisenhauer, 2009].
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 (See Section 7.3.2).
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 [Oken, 1982].
9. Must have adequate organ function as defined by the following baseline values:
•Absolute neutrophil count (ANC) ?1.5x109/L
•Hemoglobin ?9 g/dL
•Platelets ?75x109/L
•Serum bilirubin ?1.5 x upper limit of normal (ULN)
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ? 2.5xULN
•Serum Creatinine ?1.5 mg/dL (If serum creatinine is >1.5 mg/dL, calculate creatinine clearance using standard Cockcroft and Gault method (refer to Section 12.4). Creatinine clearance must be > 50 mL/min.
•Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin time (PTT) ?1.3xULN
•Left ventricular ejection fraction ? institutional lower limit of normal
10. Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to first dose of study treatment.
11. 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 64
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 28
Subjects meeting any of the following criteria must not be enrolled in the study. Deviations from the exclusion criteria are not allowed because they can potentially jeopardize the scientific integrity of the study, regulatory acceptability or subject safety. Therefore, adherence to the criteria as specified in the protocol is essential.
1. Previous treatment with a BRAF or MEK inhibitor.
2. Known ocular or primary mucosal melanoma
3. Cancer therapy (chemotherapy with delayed toxicity, radiation therapy, immunotherapy, biologic therapy, or major surgery) within the last 3 weeks; chemotherapy regimens without delayed toxicity within the last 2 weeks; or use of any investigational anti-cancer or other drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of dabrafenib.
4. Current use of a prohibited medication or is expected to require any of these medications during treatment with GSK2118436 (See Section 6.2).
5. Current use of therapeutic warfarin.
•NOTE: Low molecular weight heparin and prophylactic low-dose warfarin are permitted.
6. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, except alopecia.
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 known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of HBV clearance may be enrolled with permission of the GSK medical monitor.
9. A history of known glucose-6-phosphate dehydrogenase (G6PD) deficiency.
10. 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. History or evidence of brain metastases on MRI. If MRI is contraindicated, head CT with contrast may be performed to evaluate for brain metastases.
12. 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.
13. Uncontrolled medical conditions (i.e, diabetes mellitus, hypertension, etc), 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. Pregnant or lactating females.
15. History of alcohol or drug abuse within 6 months prior to Screening.
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