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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

June 11, 2010
March 13, 2017
July 27, 2010
January 12, 2017   (Final data collection date for primary outcome 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) ]

    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)

  • Dose-escalation phase: Safety and tolerability, dose-limiting toxicities, maximum tolerated dose (adverse events, ECG, vital signs, dermatological evaluation, haematology, serum chemistry, urinalysis) [ Time Frame: from baseline to 28 days after last dose of study drug ]
  • Pharmacokinetics: Cmax, Tmax, AUC, elimination [ Time Frame: from baseline to 28 days after last dose of stdy drug ]
  • Extension cohort: Tumour response according to RECIST criteria (best overall response rate, duration of response, progression-free survival) assessed by CT or MRI [ Time Frame: from baseline to disease progression ]
Complete list of historical versions of study NCT01143753 on ClinicalTrials.gov Archive Site
Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 7 years ]
  • Overall safety profile: Adverse events, ECG, vital signs, dermatological evaluation, haematology, serum chemistry, urinalysis [ Time Frame: through to end of study ]
  • Dose-escalating phase: Preliminary evidence of anti-tumour activity according to RECIST criteria, tumour assessments by CT/MRI [ Time Frame: from baseline to disease progression ]
  • Pharmacodynamic impact on mitogen activated protein kinase (MAPK) inhibition, assessed by tumour biopsy [ Time Frame: from baseline to disease progression ]
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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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Neoplasms
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: Continuous Dosing Cohort
    Participants will receive RO5212054 in escalating dose levels.
    Intervention: Drug: RO5212054
  • 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.
    Intervention: Drug: RO5212054
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
45
January 12, 2017
January 12, 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Denmark,   Spain
 
 
NCT01143753
NP25247
2010-018330-42 ( EudraCT Number )
Not Provided
Not Provided
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Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP