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Metastatic MelanomaPhase 4PROCLIVITY01NCT01683188

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

A Phase 4 study testing vemurafenib + HD IL-2 in people with Metastatic Melanoma, run by Clinigen, Inc. at 21 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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®). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Melanoma
What is being tested?
vemurafenib + HD IL-2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
21 sitesUnited States
Study dates
Aug 2012to Nov 2014
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 13Show fewer
  • 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.

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

United States21 sites

  • University of Michigan, Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University School of Medicine

    Atlanta, Georgia, 30322

  • Hematology/Oncology Clinic

    Baton Rouge, Louisiana, 70809

  • The Christ Hospital Cancer Center

    Cincinnati, Ohio, 45219

  • Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • St. Luke's Hospital, Anderson Campus

    Easton, Pennsylvania, 18045

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • University of Kansas

    Kansas City, Kansas, 66160-0003

  • Moores UCSD Cancer Center

    La Jolla, California, 92093

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Loyola University Medical Center, Div of Hematology/Oncology

    Maywood, Illinois, 60153

  • MSMC Research Program

    Miami Beach, Florida, 33140

  • University of Minnesota Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Luther General Cancer Care Institute

    Park Ridge, Illinois, 60068

  • UPMC Cancer Centers

    Pittsburgh, Pennsylvania, 15232

  • Providence Cancer Center

    Portland, Oregon, 97213

  • University Arizona Cancer Center

    Tucson, Arizona, 85719

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
vemurafenib + HD IL-2
Keywords
melanoma, skin cancer, Stage IV
Medical subject headings
Melanoma, Skin Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vemurafenib + HD IL-2Drug

    Also called Proleukin

Study groups in NCT01683188
Study groupRoleWhat they receive
Cohort 1OtherPatients who have received less than 7 weeks vemurafenib dosing prior to treatment with HD IL-2
Receives: Drug: vemurafenib + HD IL-2
Cohort 2OtherPatients who have receive >7 weeks to 18 weeks vemurafenib dosing prior to treatment with HD IL-2
Receives: Drug: vemurafenib + HD IL-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

    Measured: 10 weeks, 26 weeks

  2. compare safety between patients treated with vemurafenib and HD IL-2 versus historical HD IL-2 alone

    incidence of adverse events

    Measured: through study completion, an average of 1 year

Secondary outcomes (1)

  1. 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,

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Sep 2012 (estimated)
  2. Study startAug 2012
  3. Primary completionNov 2014
  4. Study completionNov 2014

Why it stopped: slow accrual led to early closure.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Other
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01683188
Sponsor's protocol ID
12PLK01
Acronym
PROCLIVITY01
Status last verified
Jan 2021
First submitted
7 Sep 2012
Last updated
1 Feb 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Clark JI, Singh J, Ernstoff MS, Lao CD, Flaherty LE, Logan TF, Curti B, Agarwala SS, Taback B, Cranmer L, Lutzky J, Luna TL, Aung S, Lawson DH. A multi-center phase II study of high dose interleukin-2 sequenced with vemurafenib in patients with BRAF-V600 mutation positive metastatic melanoma. J Immunother Cancer. 2018 Jul 27;6(1):76. doi: 10.1186/s40425-018-0387-x.

    PubMed 30053905

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing vemurafenib + HD IL-2 in people with Metastatic Melanoma, run by Clinigen, Inc. at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: slow accrual led to early closure.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01683188, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2021.

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