Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01683188
Recruitment Status : Terminated (slow accrual led to early closure.)
First Posted : September 11, 2012
Last Update Posted : February 1, 2021
Prometheus Laboratories
Information provided by (Responsible Party):
Clinigen, Inc.

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
Metastatic Melanoma 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : August 2012
Actual Primary Completion Date : November 2014
Actual Study Completion Date : November 2014

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma
Drug Information available for: Vemurafenib

Arm Intervention/treatment
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 Name: Proleukin

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 Name: Proleukin

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 [ Time Frame: 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 [ Time Frame: through study completion, an average of 1 year ]
    incidence of adverse events

Secondary Outcome Measures :
  1. Compare PFS [ Time Frame: 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,

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01683188

Show Show 21 study locations
Sponsors and Collaborators
Clinigen, Inc.
Prometheus Laboratories
Layout table for investigator information
Principal Investigator: Tharak Rao, MD Prometheus Laboratories
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Clinigen, Inc. Identifier: NCT01683188    
Other Study ID Numbers: 12PLK01
First Posted: September 11, 2012    Key Record Dates
Last Update Posted: February 1, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Clinigen, Inc.:
skin cancer
Stage IV
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action