Clinical Trials /

Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma

NCT01943422

Description:

This is a dose-seeking and efficacy study of combined BRAF Inhibitor Vemurafenib and High-dose Interferon alfa-2b for therapy of advanced melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Safety and Efficacy Study of Vemurafenib and <span class="go-doc-concept go-doc-intervention">High-dose Interferon Alfa-2b</span> in <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: Safety and Efficacy Study of Vemurafenib and High-dose Interferon Alfa-2b in Melanoma
  • Official Title: Dose-seeking and Efficacy Study of the Combination of the BRAF Inhibitor Vemurafenib and High-dose Interferon Alfa-2b for Therapy of Advanced Melanoma
  • Clinical Trial IDs

    NCT ID: NCT01943422

    ORG ID: 12-107

    Trial Conditions

    Melanoma

    Trial Interventions

    Drug Synonyms Arms
    High-dose Interferon alfa-2b IFN-2b (HDI) Vemurafenib + IFN-2b (10 MU/m2/d), Vemurafenib + IFN-2b(15 MU/m2/d), Vemurafenib + IFN-2b (20 MU/m2/d)
    Vemurafenib Zelboraf Vemurafenib + IFN-2b (10 MU/m2/d), Vemurafenib + IFN-2b(15 MU/m2/d), Vemurafenib + IFN-2b (20 MU/m2/d)

    Trial Purpose

    This is a dose-seeking and efficacy study of combined BRAF Inhibitor Vemurafenib and
    High-dose Interferon alfa-2b for therapy of advanced melanoma.

    Detailed 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) 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.

    Trial Arms

    Name Type Description Interventions
    Vemurafenib + IFN-2b (10 MU/m2/d) Experimental Vemurafenib + High-dose Interferon alfa-2b (10 MU/m2/d) IFN-2b will be administered intravenously for 5 consecutive days (Monday through Friday) every week for 4 weeks (induction) Vemurafenib will be dosed continuously at the standard Food and Drug Administration (FDA) approved dose of 960mg twice a day orally without dose interruption except for toxicities attributable to this agent. High-dose Interferon alfa-2b, Vemurafenib
    Vemurafenib + IFN-2b(15 MU/m2/d) Experimental Vemurafenib + High-dose Interferon alfa-2b (15 MU/m2/d) IFN-2b will be administered intravenously for 5 consecutive days (Monday through Friday) every week for 4 weeks (induction) Vemurafenib will be dosed continuously at the standard Food and Drug Administration (FDA) approved dose of 960mg twice a day orally without dose interruption except for toxicities attributable to this agent. High-dose Interferon alfa-2b, Vemurafenib
    Vemurafenib + IFN-2b (20 MU/m2/d) Experimental Vemurafenib + High-dose Interferon alfa-2b (20 MU/m2/d) IFN-2b will be administered intravenously for 5 consecutive days (Monday through Friday) every week for 4 weeks (induction) Vemurafenib will be dosed continuously at the standard Food and Drug Administration (FDA) approved dose of 960mg twice a day orally without dose interruption except for toxicities attributable to this agent. High-dose Interferon alfa-2b, Vemurafenib

    Eligibility Criteria

    Inclusion Criteria:

    - Patients must have a written informed consent.

    - 18 years of age.

    - Patients must have histologically confirmed recurrent stage III or stage IV melanoma
    (AJCC 7th edition classification).

    - BRAF V600E and V600K mutated

    - Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be
    excised. Adequate wound healing is required prior to study entry.

    - Patients must have measurable disease as defined by the Response Evaluation Criteria
    in Solid Tumors v1.1.

    - Patients must have adequate hematologic, renal, and liver function:

    - WBC 3,000/mm3

    - ANC 1500

    - Hb 9g/dL (women) or 11g/dL (men) (supportive transfusions will be allowed
    during induction and maintenance phases to maintain these levels)

    - Platelets 100,000/mm3 (supportive transfusions will be allowed during
    induction and maintenance phases to maintain these levels)

    - Serum Creatinine 1.5 x upper limit of normal (ULN)

    - Serum Bilirubin 1.5 x ULN

    - Serum AST/ALT 2.5 x ULN

    - EKG documenting normal intervals.

    - Fully recovered from any effects of major surgery, and be free of significant
    detectable infection.

    - ECOG performance status of 0 or 1.

    - Free of active brain metastases by contrast-enhanced CT/MRI scans within 4 weeks
    prior to starting the study drugs.

    - Female patients of child bearing potential must have a negative pregnancy test
    (within 7 days from the time of randomization).

    Exclusion Criteria:

    - 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.

    - Prior therapy (except for adjuvant immunotherapy) with a BRAF and/or MEK and/or ERK
    inhibitors.

    - 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.

    - Recent ACS/AMI - defined as within 24 weeks prior to screening.

    - Recent PCI/PTCA - defined as within 24 weeks prior to screening.

    - Recent malignant cardiac arrhythmias - all except sinus arrhythmia within 24
    weeks prior to screening.

    - Symptomatic heart failure - NYHA Class II symptoms.

    - 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.

    - Systemic steroid or other immunosuppressive therapy within 4 weeks of starting the
    study.

    - Lactating females or pregnant females.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Number of Participants with Adverse Events to determine Ph II dose

    Secondary Outcome Measures

    Progression Free and overall survival (Efficacy)

    Trial Keywords

    advanced

    melanoma

    Vemurafenib

    High-dose Interferon alfa-2b