- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02818023
Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib Advanced Melanoma
Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib for Therapy of Advanced Melanoma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- UPMC Cancer Center Hillman Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Provide written informed consent obtained prior to the initiation of study procedures.
- Male and female subjects who are at least 18 years of age.
- Histologically confirmed unresectable stage III or stage IV melanoma (AJCC 7th edition classification). Cutaneous melanoma and mucosal melanoma will be eligible.
- Only patients with BRAF V600E or V600K mutated tumors will be enrolled.
- Baseline skin exam is required for all patients. Note: Cutaneous squamous cell carcinoma (SCC) lesions identified at baseline must be excised.
- Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Baseline measurements must be obtained within 4 weeks prior to registration.
Adequate hematologic, renal, and liver function as evidenced by the following (within 4 weeks prior to starting the study drugs):
- WBC ≥ 3,000/mm3
- ANC ≥ 1500
- Hemoglobin ≥ 9g/dL (women) or ≥ 11g/dL (men) Platelets ≥ 100,000/mm3 Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
- Serum Bilirubin ≤ 1.5 x ULN
- Serum AST and ALT ≤ 2.5 x ULN
Note: (supportive transfusions will be allowed during screening and during treatment as deemed necessary by the treating physician)
- EKG documenting QTc interval < 480 msec and no clinically significant arrhythmia
- Fully recovered from any effects of major surgery, and be free of significant infection.
- ECOG performance status of 0 or 1.
- Female patients of child bearing potential must have a negative pregnancy test within 7 days from the time of registration .
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for greater than 1 year.
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
- Patients with brain metastases may be enrolled if brain metastases have been treated by surgery and/or radiation and are stable on 2 week repeat scan.
Exclusion Criteria:
- Serious clinically significant illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases (such as inflammatory bowel disease, autoimmune hepatitis, uncontrolled hypo or hyperthyroidism), severe obstructive or restrictive pulmonary diseases, retinopathy, active systemic infections, and inflammatory bowel disorders.
- Known HIV or AIDS-related illness, or active HBV and HCV.
- Has a known history of active TB (Bacillus Tuberculosis)
- History of grade 4 immune-related adverse events requiring treatment with prednisone, or grade 3 immune-related adverse events requiring prednisone >10 mg/kg for >12 weeks, if previously treated with ipilimumab.
- Prior therapy with anti-PD-1 agent(s) in the metastatic setting. Treatment with anti-PD1 in the adjuvant setting is permitted.
- Prior therapy with a BRAF and/or MEK and/or ERK inhibitors in the metastatic setting. Treatment with BRAF/MEKi in the adjuvant setting is permitted.
- Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Cardiac abnormalities
- Mean QTc interval ≥ 480 msec at screening.
- ACS/AMI -within 24 weeks prior to screening.
- PCI/PTCA -within 24 weeks prior to screening.
- Symptomatic heart failure - NYHA Class ≥ II symptoms.
- Active infection within one-week prior to study, including unexplained fever
- Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
- Lactating females and/or pregnant females.
- Any significant psychiatric disease, medical or other condition, which in the opinion of the principal investigator could prevent adequate informed consent or compromise participation in the clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Pembrolizumab plus vemurafenib and Cobimetinib
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Pembrolizumab will be given at a dose of 200 mg q3 weeks (this is the standard dosage, ). Treatment with pembrolizumab and vemurafenib will commence on the same day. One cycle of treatment will be defined as one dose of pembrolizumab and 3 weeks of vemurafenib. Vemurafenib will be given at 480 mg twice daily, 720 mg twice daily, or 960 mg twice daily. Treatment with pembrolizumab and vemurafenib will commence on the same day. One cycle of treatment will be defined as one dose of pembrolizumab and 3 weeks of vemurafenib.
Cobimetinib will be given at 20 mg once daily, 40 mg once daily, or 60 mg once daily.
Treatment with cobimetinib will commence on the same day.
Cobimetinib will be given daily for 21 days, then held for 7 days.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of participants that experience a dose-limiting toxicity
Time Frame: Up to 2 years
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determine the safety and maximum tolerated dose of vemurafenib and cobimetinib with pembrolizumab
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Up to 2 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
progression free survival
Time Frame: Up to 2 years
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Up to 2 years
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overall survival
Time Frame: up to 2 years
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up to 2 years
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overall response rate (ORR)
Time Frame: Up to 2 years
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Up to 2 years
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Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
assessment of tumor microenvironment and immune response via biomarker level measurement
Time Frame: Up to 2 years
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Up to 2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Yana M. Najjar, MD, University of Pittsburgh
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Nevi and Melanomas
- Melanoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Pembrolizumab
- Vemurafenib
Other Study ID Numbers
- 15-131
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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