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.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
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.
10 weeks, 26 weeks
United States: Food and Drug Administration
|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|