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

NCT01943422 | Completed Phase 1 DMC

• 1 other identifier: 12-107
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Melanoma

Keywords

advanced; melanoma; Vemurafenib; High-dose Interferon alfa-2b

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events to determine Ph II dose

  At each dose level, the number of patients experiencing Adverse Events over their course of treatment will be characterized by type of Adverse Event and grade using NCI CTCAE (v4.0), and by time of onset in relation to the first day of therapy.

  12-24 months from study start

Secondary Outcomes (1)

• Progression Free and overall survival (Efficacy)

  48 months

Other Outcomes (1)

• Improve tumor STAT signaling

  48 months

Study Arms (3)

Vemurafenib + IFNα-2b (10 MU/m2/d)

EXPERIMENTAL

Vemurafenib + High-dose Interferon alfa-2b (10 MU/m2/d) * IFNα-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.

Drug: High-dose Interferon alfa-2b; Drug: Vemurafenib

Vemurafenib + IFNα-2b(15 MU/m2/d)

EXPERIMENTAL

Vemurafenib + High-dose Interferon alfa-2b (15 MU/m2/d) * IFNα-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.

Drug: High-dose Interferon alfa-2b; Drug: Vemurafenib

Vemurafenib + IFNα-2b (20 MU/m2/d)

EXPERIMENTAL

Vemurafenib + High-dose Interferon alfa-2b (20 MU/m2/d) * IFNα-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.

Drug: High-dose Interferon alfa-2b; Drug: Vemurafenib

Interventions

High-dose Interferon alfa-2b DRUG

•Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects. IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.

Also known as: IFNα-2b (HDI)

Vemurafenib + IFNα-2b (10 MU/m2/d); Vemurafenib + IFNα-2b (20 MU/m2/d); Vemurafenib + IFNα-2b(15 MU/m2/d)

Vemurafenib DRUG

Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.

Also known as: Zelboraf

Vemurafenib + IFNα-2b (10 MU/m2/d); Vemurafenib + IFNα-2b (20 MU/m2/d); Vemurafenib + IFNα-2b(15 MU/m2/d)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a written informed consent.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• John Kirkwood: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Interferon alpha-2; Vemurafenib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• John Kirkwood, MD

  University of Pittsburgh Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Melanoma Program at UPCI

Study Record Dates

• First Submitted: August 27, 2013
• First Posted: September 17, 2013
• Study Start: October 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: April 3, 2018

Record last verified: 2018-04

Locations

US (1)