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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: RO5212054

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital; Oncology
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital; Medical Oncology
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hospital; Hematology and Medical Oncology
• Denmark
  • København Ø, Denmark, 2100
    • Rigshospitalet, Onkologisk Klinik
• Spain
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron; Servicio de Oncologia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RO5212054: Continuous Dosing Cohort; Participants will receive RO5212054 in escalating dose levels.	Drug: RO5212054; 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.; Other Names: PLX3603
Experimental: RO5212054: New Formulation (F05) Bridging Cohort; 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.	Drug: RO5212054; 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.; Other Names: PLX3603

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Time to Reach Maximum Plasma Concentration of RO5212054	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)	Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)
Area Under The Plasma Concentration-Time Curve of RO5212054	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)	Baseline up to cycle 10 (cycle length: 21 days) (detailed timeframe is given in description)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events	Baseline up to approximately 7 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Dienstmann R, Lassen U, Cebon J, Desai J, Brown MP, Evers S, Su F, Zhang W, Boisserie F, Lestini B, Schostack K, Meresse V, Tabernero J. First-in-Man Dose-Escalation Study of the Selective BRAF Inhibitor RG7256 in Patients with BRAF V600-Mutated Advanced Solid Tumors. Target Oncol. 2016 Apr;11(2):149-56. doi: 10.1007/s11523-015-0381-x.

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2010
• Primary Completion (Actual): June 30, 2012
• Study Completion (Actual): May 2, 2017

Study Registration Dates

• First Submitted: June 11, 2010
• First Submitted That Met QC Criteria: June 11, 2010
• First Posted (Estimate): June 14, 2010

Study Record Updates

• Last Update Posted (Actual): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: NP25247; 2010-018330-42 (EudraCT Number)