This open-label study will assess the pharmacokinetics, efficacy and safety of RO5185426 administered as 240mg tablets in previously treated patients with metastatic melanoma. Patients will be randomized to receive one of four dose-levels of RO5185426 \[RG7204; PLEXXIKON; PLX4032\] orally twice daily on days 1 to 15 (morning dose). Starting on day 22, treatment with RO5185426 may be resumed at a dose of 960 mg twice daily and continued until disease progression. Target sample size is \<100 patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Unnamed facility
La Jolla, California, United States
Unnamed facility
San Francisco, California, United States
Unnamed facility
Stanford, California, United States
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 1
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 1
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 1
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 1
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 1
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 9
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 9
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 9
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 9
Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours (AUC[0-8h]) of Vemurafenib on Day 15
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC[0-24h]) of Vemurafenib on Day 15
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24 hours post-dose on Day 15
Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC[0-168h]) of Vemurafenib on Day 15
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960 mg orally twice daily, from day 22 onward
dosage a) orally twice daily, days 1-15 (morning dose)
Unnamed facility
New Haven, Connecticut, United States
Unnamed facility
Chicago, Illinois, United States
Unnamed facility
Park Ridge, Illinois, United States
Unnamed facility
Sioux City, Iowa, United States
Unnamed facility
Omaha, Nebraska, United States
Unnamed facility
Columbus, Ohio, United States
Unnamed facility
East Providence, Rhode Island, United States
...and 3 more locations
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Time to Reach Maximum Plasma Concentration (Tmax) of Vemurafenib on Day 15
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Apparent Clearance (CL/F) of Vemurafenib on Day 15
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Terminal Elimination Half-Life (t1/2) of Vemurafenib on Day 15
Time measured for vemurafenib plasma concentrations to decrease by one-half (t1/2) was calculated as 0.693 divided by apparent first-order terminal elimination rate constant (0.693/kel).
Time frame: Pre-dose, 1, 2, 4, 5, 8, 24, 28, 72, 76, 168 hours post-dose on Day 15
Accumulation Ratio of Vemurafenib on Day 15
Accumulation ratio was calculated as, AUC(0-8) on Day 15 divided by AUC(0-8) on Day 1.
Time frame: Pre-dose, 1, 2, 4, 5, 8 hours post-dose on Day 1 and 15
Percentage of Participants With a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR)
Confirmed best overall response was defined as having best objective response as CR or PR, as assessed by investigator and confirmed at least 28 days after initial response. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1). CR was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) were required to demonstrate a reduction to normal (short axis less than \[\<\] 10 millimeters \[mm\]). PR was defined as a 30 percent (%) decrease in the sum of the diameters of the target lesions taking as a reference the baseline sum diameter. Percentage of participants with best overall response of confirmed CR or PR are reported.
Time frame: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)
Overall Survival (OS)
OS was defined as the time, in months, from the date of the first study drug administration to the date of death, regardless of the cause of death.
Time frame: Up to approximately 3 years (assessed at Cycle 1 Day 1, Cycle 3 Day 1, Cycle 5 Day 1, thereafter every 2 cycles and then every 4 cycles after Cycle 13)