A Study of RO5212054 (PLX3603) in Participants With BRAF V600-Mutated Advanced Solid Tumors

Phase 1

Completed

• Conditions: Neoplasms
• Interventions: Drug: RO5212054

• Registration Number: NCT01143753
• Lead Sponsor: Hoffmann-La Roche

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-06-11
• Study First Submitted QC: 2010-06-11
• Study First Posted: 2010-06-14
• Study Start: 2010-07-27
• Primary Completion: 2012-06-30
• Study Completion: 2017-05-02
• Status Verified: 2017-07
• Last Update Submitted: 2017-07-27
• Last Update Posted: 2017-07-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RO5212054: Continuous Dosing Cohort	RO5212054	Participants will receive RO5212054 in escalating dose levels.
RO5212054: New Formulation (F05) Bridging Cohort	RO5212054	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events	Baseline up to approximately 7 years

Trial Locations

Locations (5)

Royal Adelaide Hospital; Oncology; 🇦🇺 Adelaide, South Australia, Australia

Hospital Univ Vall d'Hebron; Servicio de Oncologia; 🇪🇸 Barcelona, Spain

Rigshospitalet, Onkologisk Klinik; 🇩🇰 København Ø, Denmark

Austin Hospital; Medical Oncology; 🇦🇺 Heidelberg, Victoria, Australia

Royal Melbourne Hospital; Hematology and Medical Oncology; 🇦🇺 Parkville, Victoria, Australia