Neoplasms
Conditions
Brief summary
This open-label, multi-center study will evaluate the safety, tolerability, and pharmacokinetics of RO5212054 \[PLX3603\] in participants with BRAF V600-mutated advanced solid tumors. Cohorts of participants will receive escalating oral doses of RO5212054. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.
Interventions
DRUGRO5212054
Participants will receive RO5212054 at a starting dose of 200 milligrams (mg) orally once daily in each 21 day cycle. Dose levels for escalation will be decided based on the safety assessment of previous cohort. Dose escalations in increments of 50-100 percent are planned.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced solid tumor * Dose-escalation phase: Histologically confirmed, newly diagnosed or relapsed/ refractory unresectable American Joint Committee on Cancer (AJCC) Stage IIIC or IV disease * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Adequate liver, renal and bone marrow function
Exclusion criteria
* Participants for whom standard therapy exists and is considered appropriate by the investigator * Prior treatment with an inhibitor of BRAF (sorafenib allowed) * Active Central nervous system (CNS) lesions, or history of or known carcinomatous meningitis * Treatment with any chemotherapy, radiotherapy, immunotherapy or investigational agent within 28 days prior to first dose of study drug * Anticipated or ongoing anti-cancer therapies other than those administered in this study * Serious cardiovascular illness within the 6 months prior to study drug administration
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Dose Limiting Toxicity | Baseline up to 21 days | — |
| Maximal Tolerated Dose of RO5212054 | Baseline up to 21 days | — |
| Maximum Plasma Concentration of RO5212054 | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | Detailed timeframe: Pre-dose (0 hour \[hr\]): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) |
| Time to Reach Maximum Plasma Concentration of RO5212054 | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) |
| Area Under The Plasma Concentration-Time Curve of RO5212054 | Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description) | Detailed timeframe: Pre-dose (0 hr): Day 1 of Cycles 1-10; Days 4, 8, 15 of Cycle 1. Post-dose: 1, 2, 4, 8, 12, 24 hr on Day 1 Cycle 1; Between 2-4 hr (1 sample) on Day 8 Cycle 1 and Day 1 Cycles 2-9; 1, 2, 4, 8, Between 10-12 hr (1 sample), 24 hr on Day 15 Cycle 1 (cycle length: 21 days) |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events | Baseline up to approximately 7 years |
Countries
Australia, Denmark, Spain
Outcome results
None listed