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HD IL-2 + Vemurafenib in Patients With BRAF Mutation Positive Metastatic Melanoma

Information source: Prometheus Laboratories
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Metastatic Melanoma

Intervention: vemurafenib + HD IL-2 (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: Prometheus Laboratories

Official(s) and/or principal investigator(s):
Tharak Rao, MD, Principal Investigator, Affiliation: Prometheus Laboratories

Summary

This is a research study to evaluate treatment of metastatic melanoma patients with a combination of drugs. The combination being studied is vemurafenib (also known as Zelboraf®) and High Dose Interleukin-2 (abbreviated as HD IL-2 and known as Proleukin®). The combination of vemurafenib and HD IL-2 immunotherapy may enhance the response.

Clinical Details

Official title: A Multi-Center Study of High Dose Aldesleukin (Interleukin-2) + Vemurafenib Therapy in Patients With BRAFV600 Mutation Positive Metastatic Melanoma

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

Primary outcome: Assess Complete Response (CR) rate in BRAFV600 mutation positive metastatic melanoma patients who have received vemurafenib plus HD IL-2 at 10 (±3) weeks and 26 (±3) weeks from the start of HD IL-2 dosing.

Detailed description: This will be an open-label, uncontrolled two-arm, multi-center study in patients with metastatic melanoma with BRAFV600 oncogene mutations. Patients will initially receive treatment with vemurafenib interspersed with two courses of High Dose IL-2 (HD IL-2). Patients are eligible for the study if they have melanoma positive for the BRAFV600 mutation, have been on vemurafenib therapy for 0-18 weeks, have responding or stable disease if on vemurafenib, and meet the requirements for dosing with HD IL-2 and all protocol inclusion and exclusion criteria. Two Cohorts will be enrolled, differing only in how they are characterized prior to HD IL-2 treatment: Cohort 1: will consist of 135 patients naïve to vemurafenib and HD IL-2 therapy. Patients in Cohort 1 will have an initial evaluation and receive a defined 6 (± 1) week course of vemurafenib before beginning HD IL-2. This Cohort will be used to define study size and statistical validity with the comparator being historic controls (using data from the BRAF positive patients from the Melanoma SELECT study Protocol IIT10PLK06). Cohort 2: will consist of up to 50 patients who have been on vemurafenib therapy for >7 to 18 weeks with stable or responding disease before starting HD IL-2. Patients in Cohort 2 will have an initial evaluation and will begin HD IL-2 treatment after >7 to 18 weeks of treatment with vemurafenib. This Cohort is designed to evaluate whether additive or synergistic clinical benefit or toxicity is observed in BRAFV600 mutation positive metastatic melanoma patients treated with vemurafenib as a single agent for >7 to18 weeks prior to the first course of HD IL-2 therapy in conjunction with continued vemurafenib. Patients in both cohorts will discontinue dosing vemurafenib prior to each treatment with HD IL-2 and resume dosing after each discharge. Patients will receive up to two courses (four cycles) of HD IL-2 and will be evaluated for their disease responses at 10 weeks (±3 weeks) from the start of HD IL-2 dosing, and 26 weeks (±3 weeks) from the start of HD IL-2 dosing. QTc intervals will be reviewed daily for changes during each cycle of HD IL-2 dosing. Administration of vemurafenib and HD IL-2 will be according to the respective Package Inserts and according to the Institution's standard of care. The investigator will determine the number of HD IL-2 cycles each patient will receive, according to the investigator's discretion and medical judgment.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female patients 18 years of age or older.

- Confirmed and measurable metastatic melanoma with the BRAFV600 mutation.

- Patients with at least one metastatic melanoma lesion accessible. for biopsy prior to

vemurafenib treatment if no archived tissue is available.

- Meet the requirements for HD IL-2 therapy per institutional guidelines.

- Meet the requirements for vemurafenib therapy per institutional guidelines.

- Patient must be willing to provide written Informed Consent and participate in study

procedures as described in the 12PLK01. Patients consented for 12PLK01 will also be asked to participate in the 10PLK13 PROCLAIM (Proleukin®) registry study. Exclusion Criteria:

- A patient will not be considered eligible for study participation if any of the

following exclusion criteria are met:

- Prior therapy of metastatic disease with any of the following: IL-2, Ipilimumab, or

other highly selective BRAF, MEK, NRAS, cMET inhibitors (e. g. GSK2118436 or GSK1120212) and TKIs.

- Exception: with a 6 week washout the following are allowed:

- Adjuvant Ipilimumab,

- Anti PD-1, Anti PD L-1

- Exclusion for Cohort 1 only: vemurafenib treatment >7 weeks.

- Exclusion for Cohort 2 only: vemurafenib treatment <7 weeks. (eligible for Cohort 1)

or >18 weeks.

- QTc interval of >500ms.

- Patients with known or suspected infection with human immunodeficiency virus (HIV),

hepatitis C virus (HCV), hepatitis B virus (HBV) or other infectious hepatitis.

- Pregnant, nursing or planning to become pregnant.

- Untreated brain metastases. (Brain metastases that have been treated, which no

longer require corticosteroid therapy and are without progression by MRI assessment at least 6 weeks after definitive therapy are acceptable.)

- Received investigational drug within 30 days prior to study dosing. Patients may

participate in non-interventional or observational clinical study (ies)

- Concomitant disease or condition that would interfere with the conduct of the study

or that would, in the opinion of the Investigator, pose an unacceptable risk to the patient in this study.

Locations and Contacts

University Arizona Cancer Center, Tucson, Arizona 85719, United States

Moores UCSD Cancer Center, La Jolla, California 92093, United States

MSMC Research Program, Miami Beach, Florida 33140, United States

Emory University School of Medicine, Atlanta, Georgia 30322, United States

Loyola University Medical Center, Div of Hematology/Oncology, Maywood, Illinois 60153, United States

Luther General Cancer Care Institute, Park Ridge, Illinois 60068, United States

Indiana University, Indianapolis, Indiana 46202, United States

University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United States

University of Kansas, Kansas City, Kansas 66160-0003, United States

Hematology/Oncology Clinic, Baton Rouge, Louisiana 70809, United States

University of Michigan, Comprehensive Cancer Center, Ann Arbor, Michigan 48109, United States

Karmanos Cancer Institute, Detroit, Michigan 48201, United States

University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota 55455, United States

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, United States

John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey 07601, United States

Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center, New York, New York 10032, United States

The Christ Hospital Cancer Center, Cincinnati, Ohio 45219, United States

Case Comprehensive Cancer Center, Cleveland, Ohio 44106, United States

Providence Cancer Center, Portland, Oregon 97213, United States

St. Luke's Hospital, Anderson Campus, Easton, Pennsylvania 18045, United States

UPMC Cancer Centers, Pittsburgh, Pennsylvania 15232, United States

Additional Information

Starting date: August 2012
Last updated: February 3, 2015

Page last updated: August 20, 2015

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