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

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: 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

Resource links provided by NLM:

MedlinePlus related topics: Melanoma

Drug Information available for: Vemurafenib

Genetic and Rare Diseases Information Center resources: Carcinoid Tumor Neuroepithelioma

U.S. FDA Resources

Further study details as provided by Plexxikon:

Primary Outcome Measures:

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.


Enrollment:	13
Study Start Date:	June 2013
Primary Completion Date:	September 2014 (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 (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

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

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


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 25, 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

ClinicalTrials.gov processed this record on September 21, 2017