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

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01143753
• Other study ID #: NP25247
• Secondary ID: 2010-018330-42
• Status: Completed
• Phase: Phase 1
• First received: June 11, 2010
• Last updated: July 27, 2017
• Start date: July 27, 2010
• Est. completion date: May 2, 2017

Study information

• Verified date: July 2017
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: May 2, 2017
• Est. primary completion date: June 30, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital; Oncology	Adelaide	South Australia
Australia	Austin Hospital; Medical Oncology	Heidelberg	Victoria
Australia	Royal Melbourne Hospital; Hematology and Medical Oncology	Parkville	Victoria
Denmark	Rigshospitalet, Onkologisk Klinik	København Ø
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Denmark,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicity		Baseline up to 21 days
Primary	Maximal Tolerated Dose of RO5212054		Baseline up to 21 days
Primary	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)
Primary	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)
Primary	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	Percentage of Participants With Adverse Events		Baseline up to approximately 7 years