Health Condition 1: null- Patients with histologically confirmed metastatic melanoma harboring the BRAF V600 mutation as determined by the cobas® 4800 BRAF V600 Mutation Test.
Conditions
Interventions
Intervention1: Vemurafenib (RO5185426): -
Intervention2: Vemurafenib: RO5185426 is a low molecular weight, orally available, selective inhibitor of the
activated form of the BRAF serine-threonine kina
Sponsors
Roche Products India Pvt Ltd
Eligibility
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Male or female patients >= 16 years of age 2. Patients with histologically confirmed metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) with documented BRAF V600 mutation determined by the cobas® 4800 BRAF V600 Mutation Test prior to administration of RO5185426. Unresectable stage IIIC disease must have confirmation from a surgical oncologist 3. Patients with either measurable or non- measurable disease(RECIST Version 1.1) 4. Patients may or may not have received prior systemic therapy for metastatic melanoma 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 6. Patients must have recovered from all side effects of their most recent systemic or local treatment for metastatic melanoma 7. Adequate hematologic, renal and liver function as defined by the following laboratory values performed within 7 days prior to first dose of RO5185426: • Absolute neutrophil count (ANC) >= 1.5 x 109/L • Platelet count >= 100 x 109/L • Hemoglobin >= 9 g/dL • Serum creatinine of normal (ULN) or creatine clearance (CrCl) > 50 mL/hr by Cockroftâ??Gault formula • Aspartate aminotransferase (AST [SGOT]) and alanine aminotransferase (ALT [SGPT]) times ULN ( to tumor) • Serum bilirubin • Alkaline phosphatase 5times ULN if considered due to tumor) 8. Negative serum pregnancy test within 7 days prior to commencement of dosing in premenopausal women. Women of non- childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >=1 year. 9. Fertile men and women must use an effective method of contraception during treatment and for at least 6 months after completion of treatment as directed by their physician. Effective methods of contraception are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly (for example implants, injectables, combined oral contraception or intra-uterine devices). At the discretion of the investigator, acceptable methods of contraception may include total abstinence in cases where the lifestyle of the patient ensures compliance.[Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.] 10.Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry 11.Signed informed consent must be obtained prior to performing any study-related procedures (includ
Exclusion criteria
Exclusion criteria: 1. Evidence of symptomatic CNS lesions as determined by investigator (patients with radiographically stable, asymptomatic lesions previously irradiated or surgically resected are eligible) 2. Patients with a previous malignancy (other than melanoma) within the past 2 years are excluded except patients with treated and controlled basal or squamous cell carcinoma (SCC) of the skin or carcinoma in-situ of the cervix. Isolated elevation in prostate- specific antigen in absence of radiographic evidence of metastatic prostate cancer is allowed 3. Concurrent administration of any anti-cancer therapies (e.g. chemotherapy, other targeted therapy, experimental drug, etc) other than those administered in this study 4. Known hypersensitivity to RO5185426 or another BRAF inhibitor 5. Pregnant or lactating women 6. Refractory nausea and vomiting,malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption. Patients must be able to swallow tablets 7. Any of the following within the 6 months prior to first RO5185426 administration: myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, hypertension not adequately controlled by current medications 8. History of congenital long QT syndrome, history or presence of clinically significant ventricular or atrial dysrhythmias >= Grade 2 (NCI CTCAE Version 4.0) 9. Corrected QT (QTc) interval >= 450 msec at baseline 10.Uncontrolled medical illness (such as infection requiring treatment with intravenous (IV) antibiotics)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To evaluate the safety and tolerability of RO5185426 in patients with metastatic melanoma (surgically incurable and unresectable stage IIIC or stage IV; AJCC) harboring the BRAF V600 mutation.Timepoint: N/A | — |
Secondary
| Measure | Time frame |
|---|---|
| To evaluate the efficacy of RO5185426 as overall response rates (ORRs) determined by the investigator (RECIST, Version 1.1) as allowed by local regulatory requirements.Timepoint: Screening, Cycle 3, Cycle 5 and End of the study. | — |
Countries
Austria, Brazil, Canada, Czech Republic, Denmark, Greece, India, Ireland, Israel, Malta, New Zealand, Portugal, Slovakia, Slovenia, Switzerland, United Kingdom, United States of America
Contacts
Public ContactDr Rupesh Pophale
Outcome results
None listed