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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01683188
Other study ID # 12PLK01
Secondary ID
Status Terminated
Phase Phase 4
First received
Last updated
Start date August 2012
Est. completion date November 2014

Study information

Verified date January 2021
Source Clinigen, Inc.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 53
Est. completion date November 2014
Est. primary completion date November 2014
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
vemurafenib + HD IL-2


Locations

Country Name City State
United States University of Michigan, Comprehensive Cancer Center Ann Arbor Michigan
United States Emory University School of Medicine Atlanta Georgia
United States Hematology/Oncology Clinic Baton Rouge Louisiana
United States The Christ Hospital Cancer Center Cincinnati Ohio
United States Case Comprehensive Cancer Center Cleveland Ohio
United States Karmanos Cancer Institute Detroit Michigan
United States St. Luke's Hospital, Anderson Campus Easton Pennsylvania
United States John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey
United States Indiana University Indianapolis Indiana
United States University of Iowa Hospitals and Clinics Iowa City Iowa
United States University of Kansas Kansas City Kansas
United States Moores UCSD Cancer Center La Jolla California
United States Dartmouth-Hitchcock Medical Center Lebanon New Hampshire
United States Loyola University Medical Center, Div of Hematology/Oncology Maywood Illinois
United States MSMC Research Program Miami Beach Florida
United States University of Minnesota Masonic Cancer Center Minneapolis Minnesota
United States Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center New York New York
United States Luther General Cancer Care Institute Park Ridge Illinois
United States UPMC Cancer Centers Pittsburgh Pennsylvania
United States Providence Cancer Center Portland Oregon
United States University Arizona Cancer Center Tucson Arizona

Sponsors (2)

Lead Sponsor Collaborator
Clinigen, Inc. Prometheus Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Assess Complete Response (CR) rate in BRAFV600 mutation positive metastatic melanoma patients who have received vemurafenib plus HD IL-2 at 10 (±3) weeks from the start of HD IL-2 dosing to assess initial response and 26 (±3) weeks to assess and change assessment of tumor response in patients with CR or near CR (> 90%) after discontinuation of vemurafenib, based on RECIST criteria 10 weeks, 26 weeks
Primary compare safety between patients treated with vemurafenib and HD IL-2 versus historical HD IL-2 alone incidence of adverse events through study completion, an average of 1 year
Secondary Compare PFS compare progression free survival (PFS) from initiation of vemurafenib between Cohort 1 and Cohort 2 patients, compare overall PFS with the historical data using vemurafenib or HD IL-2 alone, 1 year
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