Metastatic Melanoma MedDRA version: 14.1 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Product Code: RO5185426/F20
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Vemurafenib
CAS Number: 918504-65-1
Current Sponsor code: RO5185426-006
Other descriptive name: RG7204, PLX4032
Sponsors
F. Hoffman-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with histologically confirmed surgically incurable and unresectable stage IIIC or stage IV (AJCC) melanoma. Unresectable stage IIIC disease must have confirmation from a surgical oncologist. 2.Patients must have a positive BRAF mutation result determined by a Roche-designated central reference laboratory using the cobas® 4800 BRAF V600 Mutation Test prior to administration of vemurafenib. 3.Patients may have newly diagnosed melanoma or have completed and failed prior standard of care regimen (e.g., DTIC, temozolomide, etc.). 4.Measurable disease according to RECIST criteria Version 1.1 5. Must have a head CT/MRI to evaluate for CNS metastasis within 28 days prior to treatment. Patients with radiographically stable, asymptomatic previously treated lesions are eligible provided: -Patient has received prior treatment [including radiation therapy (whole brain radiotherapy is not allowed with the exception of patients who have also had definitive resection or stereotactic therapy of all radiologically detectable parenchymal lesions), stereotactic radiosurgery, surgical resection] to the site(s) of CNS metastatic disease = 3 months prior to starting study treatment -Patient has no requirement for glucocorticoids, and discontinued = 21 days prior to starting study treatment - Patient is not taking anticonvulsants (discontinued at least 3 weeks prior to treatment) 6.Patients aged = 12 to = 17 years 7.Performance Status: Karnofsky performance score of 50-100 (for patients =16 years of age) or Lansky score of = 60 (for patients 3 months. 10. Adequate hematologic, renal and liver function as defined by laboratory values performed within 28 days prior to initiation of dosing. 11.Completed baseline skin exam by a dermatologist for cutaneous squamous cell carcinoma. Exam must be negative or if, suspected cutaneous SCC lesions are identified they must be excised, and there must be adequate wound healing prior to study treatment. Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Patients with active or untreated CNS lesions 2.History of or known spinal cord compression, or carcinomatous meningitis. 3.Negative result for BRAF mutation as determined using the cobas® 4800 BRAF V600 Mutation Test 4.Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study. 5.Patients with a previous malignancy within the past 5 years are excluded except for patients with basal or squamous cell carcinoma (SCC) of the skin, melanoma in-situ, and carcinoma in-situ of the cervix. 6.Patients who have been previously treated with a selective/specific BRAF or MEK inhibitor (previous treatment with sorafenib is allowed). 7.Patients who have had any previous treatment with study drug (vemurafenib) or participated in a clinical trial that includes vemurafenib. 8.QTc >450 msec on screening ECG or history of congential long QT syndrome. 9.NCI-CTCAE Version 4.0 grade 3 hemorrhage within 4 weeks of starting the study treatment. 10.Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, serious cardiac arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident or transient ischemic attack, or symptomatic pulmonary embolism. 11.Known clinically significant active infection at the time of study treatment start, at the time of screening or within 14 days of study drug start. 12.History of allogeneic bone marrow transplantation or organ transplantation. of the investigator would make the patient inappropriate for entry into this study. 13.Known HIV positivity or AIDS-related illness, or active HBV, and active HCV.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose-escalation phase: To estimate the MTD and to identify the recommended dose of vemurafenib in pediatric patients aged 12 through 17 years with newly diagnosed or recurrent unresectable Stage IIIC or Stage IV BRAF mutation–positive melanoma;Secondary Objective: Dose-escalation and extension phases: To describe the pharmacokinetics of vemurafenib in pediatric patients aged 12 through 17 years with BRAF mutation–positive newly diagnosed unresectable Stage IIIC or Stage IV or recurrent melanoma Dose-escalation and extension phases: To evaluate the safety and tolerability of vemurafenib using NCI CTCAE v4.0 in pediatric patients aged 12 through 17 years with newly diagnosed or recurrent BRAF mutation–positive unresectable Stage IIIC or Stage IV melanoma Dose-escalation and extension phases: To evaluate the efficacy of vemurafenib in patients treated at the recommended dose using investigator-assessed BORR, based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1), PFS, OS, and clinical benefit rate (CBR);Primary end point(s): The primary efficacy variable for this study is the rate of best overall response (BORR) assessed by the investigators according to the RECIST criteria (Version. 1.1). The BORR is defined as the number of patients whose best objective response is complete response (CR) or partial response (PR) divided by the total number of intent-to-treat patients. intent-to-treat patients are defined in 8.2.1. Patients with no post baseline tumor assessments and have not died will be considered as non-responders.;Timepoint(s) of evaluation of this end point: Baseline total tumor burden must be assessed within a maximum of 4 weeks before first dose of study drug treatment. The first post start of treatment tumor assessment is scheduled at week 4. Subsequent tumor assessments will be performed every 8 weeks for the first 12 cycles and every 12 weeks, thereafter until disease progression, death due to any cause, unaccept | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Clinical benefit rate (CBR), PFS, OS, and duration of response.;Timepoint(s) of evaluation of this end point: CBR and Duration of Response: Baseline total tumor burden must be assessed within a maximum of 4 weeks before first dose of study drug treatment. The first post start of treatment tumor assessment is scheduled at week 4. Subsequent tumor assessments will be performed every 8 weeks for the first 12 cycles and every 12 weeks, thereafter until disease progression, death due to any cause, unacceptable toxicity, discontinuation from the study. PFS: Interval between the day of first treatment and the first documentation of progressive disease or death. OS: Time from the date of first treatment to the date of death | — |
Countries
Australia, Brazil, Germany, Italy, Poland, Slovakia, Spain, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd.
Outcome results
None listed