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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01143753
First received: June 11, 2010
Last updated: March 13, 2017
Last verified: March 2017
  Purpose
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.

Condition Intervention Phase
Neoplasms Drug: RO5212054 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
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

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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) ]

    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 [ Time Frame: 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 [ Time Frame: 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:
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 7 years ]

Enrollment: 45
Actual Study Start Date: July 27, 2010
Study Completion Date: January 12, 2017
Primary Completion Date: January 12, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: PLX3603

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01143753

Locations
Australia, South Australia
Royal Adelaide Hospital; Oncology
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Austin Hospital; Medical Oncology
Heidelberg, Victoria, Australia, 3084
Royal Melbourne Hospital; Hematology and Medical Oncology
Parkville, Victoria, Australia, 3052
Denmark
Rigshospitalet, Onkologisk Klinik
København Ø, Denmark, 2100
Spain
Hospital Univ Vall d'Hebron; Servicio de Oncologia
Barcelona, Spain, 08035
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01143753     History of Changes
Other Study ID Numbers: NP25247
2010-018330-42 ( EudraCT Number )
Study First Received: June 11, 2010
Last Updated: March 13, 2017

ClinicalTrials.gov processed this record on June 23, 2017