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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by Plexxikon
Sponsor:
Information provided by (Responsible Party):
Plexxikon
ClinicalTrials.gov Identifier:
NCT01826448
First received: April 1, 2013
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
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
Drug: PLX3397
Drug: vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Plexxikon:

Primary Outcome Measures:
  • Safety-Subject incidence of adverse events [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Patients will be followed every 3 months for overall survival.


Estimated Enrollment: 90
Study Start Date: June 2013
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: PLX3397 Drug: vemurafenib
Other Name: Zelboraf
Experimental: Cohort 3
Patients will take 1000mg/day of PLX3397 and 960mg BID of vemurafenib
Drug: PLX3397 Drug: vemurafenib
Other Name: Zelboraf
Experimental: Cohort 2
Patients will take 800mg/day of PLX3397 and 960mg BID of vemurafenib
Drug: PLX3397 Drug: vemurafenib
Other Name: Zelboraf
Experimental: Cohort 1
Patients will take 800mg/day of PLX3397 and 720mg BID of vemurafenib
Drug: PLX3397 Drug: vemurafenib
Other Name: Zelboraf

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01826448

Contacts
Contact: Henry Hsu, MD hhsu@plexxikon.com

Locations
United States, California
UCLA Recruiting
Los Angeles, California, United States, 90024
Principal Investigator: Antoni Ribas, MD         
United States, Colorado
University of Colorado, Denver Not yet recruiting
Aurora, Colorado, United States, 80012
Principal Investigator: Rene Gonzalez, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37232
Principal Investigator: Jeffrey A Sosman, MD         
United States, Washington
Seattle Cancer Care Alliance Not yet recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Kim A Margolin, MD         
France
Institute Gustave Roussy Not yet recruiting
Paris, France
Principal Investigator: Caroline Robert, MD         
Germany
University Hospital Essen Not yet recruiting
Essen, Germany
Principal Investigator: Dirk Schadendorf, MD         
Sponsors and Collaborators
Plexxikon
  More Information

No publications provided

Responsible Party: Plexxikon
ClinicalTrials.gov Identifier: NCT01826448     History of Changes
Other Study ID Numbers: PLX108-09
Study First Received: April 1, 2013
Last Updated: September 6, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on August 18, 2014