Recruitment

Recruitment Status
Completed
Estimated Enrollment
63

Inclusion Criterias

Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1.
Serum AST/ALT ≤ 2.5 x ULN
Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
...
Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1.
Serum AST/ALT ≤ 2.5 x ULN
Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
ECOG performance status of 0 or 1.
EKG documenting normal intervals.
Platelets ≥ 100,000/mm3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
Female patients of child bearing potential must have a negative pregnancy test (within 7 days from the time of randomization).
Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
Free of active brain metastases by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs.
Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification).
ANC ≥ 1500
Fully recovered from any effects of major surgery, and be free of significant detectable infection.
Patients must have a written informed consent.
BRAF V600E and V600K mutated
WBC ≥ 3,000/mm3
Serum Bilirubin ≤ 1.5 x ULN
Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. Adequate wound healing is required prior to study entry.
18 years of age.

Exclusion Criterias

Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
Recent ACS/AMI - defined as within 24 weeks prior to screening.
...
Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
Recent ACS/AMI - defined as within 24 weeks prior to screening.
Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or MEK and/or ERK inhibitors.
Recent PCI/PTCA - defined as within 24 weeks prior to screening.
Active infection or antibiotics within one-week prior to study, including unexplained fever Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial.
Recent malignant cardiac arrhythmias - all except sinus arrhythmia within 24 weeks prior to screening.
Mean QTc interval ≥ 480 msec at screening.
Symptomatic heart failure - NYHA Class ≥ II symptoms.
Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders. This includes known HIV or AIDS-related illness, or active HBV and HCV.
Lactating females or pregnant females.

Summary

Conditions
Melanoma
Type
Interventional
Phase
Phase 1
Design
  • Allocation: Non-Randomized
  • Intervention Model: Single Group Assignment
  • Masking: None (Open Label)
  • Primary Purpose: Treatment

Participation Requirements

Age
Between 18 years and 125 years
Gender
Both males and females

Description

Dose-selection and dose-expansion study of combination therapy with high-dose interferon alfa-2b and vemurafenib. Vemurafenib at standard dosing with a 2 week lead-in period to exploit potential immunomodulatory effects. Concurrent HDI following this (week 2 onwards) at standard induction (4 weeks) ...

Dose-selection and dose-expansion study of combination therapy with high-dose interferon alfa-2b and vemurafenib. Vemurafenib at standard dosing with a 2 week lead-in period to exploit potential immunomodulatory effects. Concurrent HDI following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses. Modified Storer's "up and down" dose escalation schema using 3 fixed dose levels for HDI and a fixed sample size that allows efficient identification of recommended phase II dose. 36-63 patients will be enrolled depending on toxicity parameters. oIn the dose-selection portion, 3 patients will be enrolled per dose level, starting from the lowest dose level. Enrollment will occur serially allowing for the observation of toxicity during the observation period. oIterative enrollment of up to 3 subjects per cohort will be continued until a total of 30 evaluable subjects have been enrolled. oThe dose level at which the RLT rate is the closest to 1/3 will be considered as RP2D. oDuring the dose-expansion portion of the trial, depending on the number of patients treated at RP2D during the dose-selection portion, additional patients may be enrolled - the accrual target is 36 patients treated at RP2D.

Inclusion Criterias

Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1.
Serum AST/ALT ≤ 2.5 x ULN
Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
...
Patients must have measurable disease as defined by the Response Evaluation Criteria in Solid Tumors v1.1.
Serum AST/ALT ≤ 2.5 x ULN
Hb ≥ 9g/dL (women) or ≥ 11g/dL (men) (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
ECOG performance status of 0 or 1.
EKG documenting normal intervals.
Platelets ≥ 100,000/mm3 (supportive transfusions will be allowed during induction and maintenance phases to maintain these levels)
Female patients of child bearing potential must have a negative pregnancy test (within 7 days from the time of randomization).
Serum Creatinine ≤ 1.5 x upper limit of normal (ULN)
Free of active brain metastases by contrast-enhanced CT/MRI scans within 4 weeks prior to starting the study drugs.
Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification).
ANC ≥ 1500
Fully recovered from any effects of major surgery, and be free of significant detectable infection.
Patients must have a written informed consent.
BRAF V600E and V600K mutated
WBC ≥ 3,000/mm3
Serum Bilirubin ≤ 1.5 x ULN
Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. Adequate wound healing is required prior to study entry.
18 years of age.

Exclusion Criterias

Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
Recent ACS/AMI - defined as within 24 weeks prior to screening.
...
Refractory nausea, vomiting, small bowel resection or any other gastrointestinal ailment that would preclude study drug absorption.
Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the study.
Recent ACS/AMI - defined as within 24 weeks prior to screening.
Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or MEK and/or ERK inhibitors.
Recent PCI/PTCA - defined as within 24 weeks prior to screening.
Active infection or antibiotics within one-week prior to study, including unexplained fever Any significant psychiatric disease, medical intervention, or other condition, which in the opinion of the principal investigator, could prevent adequate informed consent or compromise participation in the clinical trial.
Recent malignant cardiac arrhythmias - all except sinus arrhythmia within 24 weeks prior to screening.
Mean QTc interval ≥ 480 msec at screening.
Symptomatic heart failure - NYHA Class ≥ II symptoms.
Serious illnesses, such as: cardiovascular disease (uncontrolled congestive heart failure, uncontrolled hypertension, cardiac ischemia, myocardial infarction, and severe cardiac arrhythmia), bleeding disorders, symptomatic autoimmune diseases, severe obstructive or restrictive pulmonary diseases, uncontrolled endocrine disorders (hypothyroidism, hyperthyroidism and diabetes mellitus), retinopathy, active systemic infections, and inflammatory bowel disorders. This includes known HIV or AIDS-related illness, or active HBV and HCV.
Lactating females or pregnant females.

Locations

Pittsburgh, Pennsylvania, 15232
Pittsburgh, Pennsylvania, 15232

Tracking Information

NCT #
NCT01943422
Collaborators
Merck Sharp & Dohme Corp.
Investigators
  • Principal Investigator: John Kirkwood, MD University of Pittsburgh Medical Center
  • John Kirkwood, MD University of Pittsburgh Medical Center