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PROCLIVITY01: HD IL-2 + Vemurafenib in Patients With BRAF Mutation Positive Metastatic Melanoma

Sponsor
Clinigen, Inc. (Industry)
Overall Status
Terminated
CT.gov ID
NCT01683188
Collaborator
Prometheus Laboratories (Industry)
53
Enrollment
21
Locations
2
Arms
27
Duration (Months)
2.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: vemurafenib + HD IL-2
 Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
53 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Multi-Center Study of High Dose Aldesleukin (Interleukin-2) + Vemurafenib Therapy in Patients With BRAFV600 Mutation Positive Metastatic Melanoma
Study Start Date :
Aug 1, 2012
Actual Primary Completion Date :
Nov 1, 2014
Actual Study Completion Date :
Nov 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Other: Cohort 1

Patients who have received less than 7 weeks vemurafenib dosing prior to treatment with HD IL-2

Drug: vemurafenib + HD IL-2
Other Names:
  • Proleukin

    		•
    Other: Cohort 2

    Patients who have receive >7 weeks to 18 weeks vemurafenib dosing prior to treatment with HD IL-2

    Drug: vemurafenib + HD IL-2
    Other Names:
  • Proleukin

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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 [10 weeks, 26 weeks]

      assessment of tumor response in patients with CR or near CR (> 90%) after discontinuation of vemurafenib, based on RECIST criteria

    2. compare safety between patients treated with vemurafenib and HD IL-2 versus historical HD IL-2 alone [through study completion, an average of 1 year]

      incidence of adverse events

    Secondary Outcome Measures

    1. Compare PFS [1 year]

      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,

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Arizona Cancer Center Tucson Arizona United States 85719
    2 Moores UCSD Cancer Center La Jolla California United States 92093
    3 MSMC Research Program Miami Beach Florida United States 33140
    4 Emory University School of Medicine Atlanta Georgia United States 30322
    5 Loyola University Medical Center, Div of Hematology/Oncology Maywood Illinois United States 60153
    6 Luther General Cancer Care Institute Park Ridge Illinois United States 60068
    7 Indiana University Indianapolis Indiana United States 46202
    8 University of Iowa Hospitals and Clinics Iowa City Iowa United States 52242
    9 University of Kansas Kansas City Kansas United States 66160-0003
    10 Hematology/Oncology Clinic Baton Rouge Louisiana United States 70809
    11 University of Michigan, Comprehensive Cancer Center Ann Arbor Michigan United States 48109
    12 Karmanos Cancer Institute Detroit Michigan United States 48201
    13 University of Minnesota Masonic Cancer Center Minneapolis Minnesota United States 55455
    14 Dartmouth-Hitchcock Medical Center Lebanon New Hampshire United States 03756
    15 John Theurer Cancer Center at Hackensack University Medical Center Hackensack New Jersey United States 07601
    16 Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    17 The Christ Hospital Cancer Center Cincinnati Ohio United States 45219
    18 Case Comprehensive Cancer Center Cleveland Ohio United States 44106
    19 Providence Cancer Center Portland Oregon United States 97213
    20 St. Luke's Hospital, Anderson Campus Easton Pennsylvania United States 18045
    21 UPMC Cancer Centers Pittsburgh Pennsylvania United States 15232

    Sponsors and Collaborators

    • Clinigen, Inc.
    • Prometheus Laboratories

    Investigators

    • Principal Investigator: Tharak Rao, MD, Prometheus Laboratories

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Clinigen, Inc.
    ClinicalTrials.gov Identifier:
    NCT01683188
    Other Study ID Numbers:
    • 12PLK01
    First Posted:
    Sep 11, 2012
    Last Update Posted:
    Feb 1, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Clinigen, Inc.
    melanoma
    skin cancer
    Stage IV
    Additional relevant MeSH terms:
    Melanoma
    Vemurafenib

    Study Results

    No Results Posted as of Feb 1, 2021