This open-label, multicenter. single arm Phase I dose-escalation study with efficacy tail extension will evaluate the maximum tolerated dose/recommended dose, the safety and efficacy of vemurafenib (RO5185426) in pediatric participants (aged 12 through 17) with newly diagnosed or recurrent surgically incurable and unresectable Stage IIIC or Stage IV melanoma harboring BRAFV600 mutations. Participants will receive vemurafenib orally twice daily until disease progression or unacceptable toxicity occurs.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Cohort 1 (participants \>=45 kg): starting dose level 720mg; next dose level 960 mg Cohort 2 (participants \<45 kg): starting dose 480 mg
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Aurora, Colorado, United States
Maximum Tolerated Dose (MTD)/Recommended Dose
The MTD was defined as the dose level at which six evaluable participants had been treated and at most one participant experienced a dose limiting toxicity (DLT) and the next highest dose level was too toxic. Dose escalation occurred if 0 out of 3 or at most 1 out of 6 participant experienced DLT while being treated at a dose level; otherwise the dose was declared unsafe and thus above the MTD.
Time frame: Up to 28 days of treatment
Area Under the Concentration-Time Curve for Vemurafenib
Time frame: Pre-dose, 2, 4, 8, 12 hours post dose on Cycle 1 Day 1 and Cycle 1 Day 22 (each cycle is of 28 days)
Number of Participants With an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a patient administered a pharmaceutical product and which did not necessarily have to have a causal relationship with study treatment.
Time frame: Up to approximately 2 years 11 months
Best Overall Response Rate (BORR)
BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants who achieved a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a \>=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.
Time frame: Up to 2 years
Clinical Benefit Rate (CBR)
CBR was defined as the number of participants that achieved a CR, PR or stable disease (SD) (SD for at least 6 weeks) as assessed by investigators according to the RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as at \>=30% decrease under baseline of the sum of diameters of all target lesions. SD was defined as steady state of disease with neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD).
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Unnamed facility
Saint Petersburgh, Florida, United States
Unnamed facility
Bethesda, Maryland, United States
Unnamed facility
Boston, Massachusetts, United States
Unnamed facility
New York, New York, United States
Unnamed facility
Memphis, Tennessee, United States
Unnamed facility
Houston, Texas, United States
Unnamed facility
Westmead, New South Wales, Australia
Unnamed facility
Brisbane, Queensland, Australia
...and 16 more locations
Time frame: Up to 2 years
Progression-free Survival (PFS)
PFS was defined as the time between the day of first treatment and the first documentation of progressive disease or death. Progression was defined as a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Participants who were withdrawn from the study without documented progression were to be censored at the date of the last known tumor assessment when the participant was known to be progression free. Median PFS was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
Time frame: Randomization date of first subject until disease progression or death or which ever occur first (2 years)
Overall Survival (OS)
Overall survival was defined as the time between the date of first treatment to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of their last being known alive. Median overall survival was estimated using Kaplan-Meier method and 95% CI for median was computed using the Brookmeyer and Crowley method.
Time frame: Randomization date of first subject until death (2 years)