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

Metastatic Melanoma Clinical Trial

— PROCLIVITY01  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01683188
• Other study ID #: 12PLK01
• Status: Terminated
• Phase: Phase 4
• 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
• 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.

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma

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