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A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01826448
Recruitment Status : Terminated (No activity was observed. BRAFi-naïve participants should have received triple combination treatment (including MEK inhibitor). Continuation was not justified.)
First Posted : April 8, 2013
Results First Posted : May 28, 2020
Last Update Posted : May 28, 2020
Sponsor:
Collaborator:
Plexxikon
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE April 1, 2013
First Posted Date  ICMJE April 8, 2013
Results First Submitted Date  ICMJE May 12, 2020
Results First Posted Date  ICMJE May 28, 2020
Last Update Posted Date May 28, 2020
Actual Study Start Date  ICMJE November 5, 2013
Actual Primary Completion Date September 22, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2020)
Percentage of Participants With Adverse Events Who Received PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 3, 2013)
  • Safety-Subject incidence of adverse events [ Time Frame: 1 year ]
    Subjects will take oral doses of PLX3397 and vemurafenib twice a day. Physical examinations, vital signs, 12-lead electrocardiograms (ECG), adverse events, hematology and serum chemistry will be used to assess safety throughout the study. Adverse events will be monitored and reviewed for safety issues/abnormal changes in the above mentioned tests.
  • Overall response rate - for those patients taking PLX3397 and vemurafenib at the recommended phase 2 dose. [ Time Frame: 1 year ]
    Patients will have CT scans every 6 weeks for the first 12 weeks and every 9 weeks thereafter. Response to treatment will be evaluated using RECIST 1.1 criteria.
  • Response Duration - for those patients taking PLX3397 and vemurafenib at the recommended phase 2 dose. [ Time Frame: 1 year ]
    CT scans will be taken every 6 weeks for the first 12 weeks and every 9 weeks thereafter. Response duration is defined as number of days from date of initial response to date of first documented disease progression or death, whichever occurs first.
  • progression free survival (PFS)-for those patients taking PLX3397 and vemurafenib at the recommended phase 2 dose. [ Time Frame: 1 year ]
    CT scans will be taken every 6 weeks for the first 12 weeks and then every 9 weeks therafter. PFS will be calculated as the number of days from first day of treatment to date of first documented disease progression or date of death, whichever comes first.
  • overall survival- for those patients taking PLX3397 and vemurafenib at the recommended phase 2 dose. [ Time Frame: 1 year ]
    Patients will be followed every 3 months for overall survival.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1b Open Label, Dose Escalation Study of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Melanoma
Official Title  ICMJE A Phase 1b Open Label, Dose Escalation Study to Assess Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of PLX3397 in Combination With Vemurafenib in V600-mutated BRAF Unresectable or Metastatic Melanoma
Brief Summary The purpose of this research study is to test the safety of an investigational new drug called PLX3397 when used in combination with Vemurafenib (Zelboraf™) at different dose levels. Vemurafenib has been approved by the United States Food and Drug Administration (FDA)/European Medicines Agency (EMA) for the treatment of a specific category of unresectable or metastatic melanoma.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • V600-mutated BRAF Unresectable Melanoma
  • V600-mutated BRAF Metastatic Melanoma
  • Stage III or Stage IV Metastatic Melanoma That Has Not Been Previously Treated With a Selective BRAF Inhibitor
Intervention  ICMJE
  • Drug: PLX3397
  • Drug: vemurafenib
    Other Name: Zelboraf
Study Arms  ICMJE
  • Experimental: Dose extension cohort
    Patients will take PLX3397 and vemurafenib at the recommended phase 2 dose. This will be determined by the tolerability and safety of these drugs in the previous 3 cohorts.
    Interventions:
    • Drug: PLX3397
    • Drug: vemurafenib
  • Experimental: Cohort 3
    Patients will take 1000mg/day of PLX3397 and 960mg BID of vemurafenib
    Interventions:
    • Drug: PLX3397
    • Drug: vemurafenib
  • Experimental: Cohort 2
    Patients will take 800mg/day of PLX3397 and 960mg BID of vemurafenib
    Interventions:
    • Drug: PLX3397
    • Drug: vemurafenib
  • Experimental: Cohort 1
    Patients will take 800mg/day of PLX3397 and 720mg BID of vemurafenib
    Interventions:
    • Drug: PLX3397
    • Drug: vemurafenib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 25, 2014)
13
Original Estimated Enrollment  ICMJE
 (submitted: April 3, 2013)
90
Actual Study Completion Date  ICMJE September 22, 2014
Actual Primary Completion Date September 22, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Male or female ≥18 years old.
  • Patients with histologically confirmed unresectable Stage III or Stage IV metastatic melanoma who have not been previously treated with a selective BRAF inhibitor.
  • Presence of a BRAF V600 mutation in the tumor tissue using the cobas BRAF mutation assay or comparable standard of care methodology.
  • Measurable disease per RECIST v. 1.1 criteria.
  • ECOG performance status 0 or 1.

Exclusion Criteria:

  • Radiation therapy within 14 days of C1D1.
  • Investigational drug use within 28 days of C1D1.
  • Patients with active CNS lesions are excluded (i.e., those with radiographically unstable, symptomatic lesions). However, patients treated with stereotactic therapy or surgery are eligible if they remain without evidence of disease progression in the brain for ≥3 weeks.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01826448
Other Study ID Numbers  ICMJE PLX108-09
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE Plexxikon
Investigators  ICMJE Not Provided
PRS Account Daiichi Sankyo, Inc.
Verification Date May 2020

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