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

Study Description

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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.

Condition or disease	Intervention/treatment	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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	13 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	June 2013
Actual Primary Completion Date :	September 2014

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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Locations

United States, California
UCLA
Los Angeles, California, United States, 90024
United States, Colorado
University of Colorado, Denver
Aurora, Colorado, United States, 80012
United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
France
Institute Gustave Roussy
Paris, France
Germany
University Hospital Essen
Essen, Germany

Sponsors and Collaborators

Plexxikon

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Plexxikon
ClinicalTrials.gov Identifier:	NCT01826448 History of Changes
Other Study ID Numbers:	PLX108-09
First Posted:	April 8, 2013
Last Update Posted:	September 29, 2014
Last Verified:	September 2014

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; Vemurafenib; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action