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

Phase 4
18 Years
Open (Enrolling)
Metastatic Melanoma

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Trial Information

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

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

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.

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 and 10PLK13 protocols.

Exclusion Criteria:

- Prior therapy with any of the following: IL-2, Ipilimumab, or other highly selective
BRAF, MEK, NRAS, PD 1, cMET inhibitors (e.g. GSK2118436 or GSK1120212) and TKIs.

- 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 studies; participation in
the 10PLK13 registry study is a requirement for enrollment in 12PLK01.

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label

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 and 26 (±3) weeks from the start of HD IL-2 dosing.

Outcome Time Frame:

10 weeks, 26 weeks

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

Related Keywords:

  • Metastatic Melanoma
  • melanoma
  • skin cancer
  • Stage IV
  • Melanoma



University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Rush University Medical Center Chicago, Illinois  60612-3824
Emory University School of Medicine Atlanta, Georgia  30322
Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756
UPMC Cancer Centers Pittsburgh, Pennsylvania  15232
Moores UCSD Cancer Center La Jolla, California  92093-0658
John Theurer Cancer Center at Hackensack University Medical Center Hackensack, New Jersey  07601
Karmanos Cancer Institute Detroit, Michigan  48201
Providence Cancer Center Portland, Oregon  97213-2933
University of Minnesota Masonic Cancer Center Minneapolis, Minnesota  55455
MSMC Research Program Miami Beach, Florida  33140
Loyola University Medical Center, Div of Hematology/Oncology Maywood, Illinois  60153
St. Luke's Hospital, Anderson Campus Easton, Pennsylvania  18045