Overview

This trial has been completed.

Condition neoplasms
Treatment ro5212054
Phase phase 1
Sponsor Hoffmann-La Roche
Start date July 2010
End date January 2017
Trial size 45 participants
Trial identifier NCT01143753, 2010-018330-42, NP25247

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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation non-randomized
Intervention model parallel assignment
Primary purpose treatment
Masking no masking
Arm
(Experimental)
Participants will receive RO5212054 in escalating dose levels.
ro5212054 PLX3603
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.
(Experimental)
Participants will receive RO5212054 as a single dose of new formulation (F05-150 mg film-coated tablet with different ratios of ingredients than F03 to increase bioavailability) and a single dose of current clinical Formulation (F03-150 mg film-coated tablet) in a cross-over manner. Participants will be alternately assigned to receive either F05 or F03 as their first dose, followed by the opposite Formulation as their second dose. Dose of RO5212054 will be decided based on the results of continuous dosing cohort.
ro5212054 PLX3603
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.

Primary Outcomes

Measure
Percentage of Participants With Dose Limiting Toxicity
time frame: Baseline up to 21 days
Maximal Tolerated Dose of RO5212054
time frame: Baseline up to 21 days
Maximum Plasma Concentration of RO5212054
time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Time to Reach Maximum Plasma Concentration of RO5212054
time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Area Under The Plasma Concentration-Time Curve of RO5212054
time frame: Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)

Secondary Outcomes

Measure
Percentage of Participants With Adverse Events
time frame: Baseline up to approximately 7 years

Eligibility Criteria

All participants at least 18 years old.

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

Additional Information

Official title An Open-Label, Multiple Ascending Dose (MAD) Study of the Selective BRAF Inhibitor RO5212054 (PLX3603) to Evaluate Safety, Tolerability and Pharmacokinetics in Patients With BRAF V600-Mutated Advanced Solid Tumours
Trial information was received from ClinicalTrials.gov and was last updated in March 2017.
Information provided to ClinicalTrials.gov by Hoffmann-La Roche.