|Phase IV||Treatment||Active||18 and over||Other||12PLK01|
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.
Further Study Information
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.
- 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.
- 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.
Trial Lead Organizations/Sponsors
Prometheus Therapeutics and Diagnostics
|Theresa Luna||Ph: 858-882-8058|
|Arizona Cancer Center at University of Arizona Health Sciences Center|
|Amy Bauland||Ph: 520-694-0859|
|Lee Duncan Cranmer||Principal Investigator|
|Rebecca and John Moores UCSD Cancer Center|
|Suzanna Lee, MPH||Ph: 858-822-4171|
|Gregory A. Daniels||Principal Investigator|
|MSMC Research Program|
|Yvonne Nunez, BSHSA||Ph: 305-674-2625|
|Jose Lutzky, MD||Principal Investigator|
|Winship Cancer Institute of Emory University|
|Tatiana Kurilo, MPH||Ph: 404-778-1842|
|David Lawson, MD||Principal Investigator|
|Loyola University Medical Center, Div of Hematology/Oncology|
|Ann L Clark, RN, BSN, MSN, CCRC, CCRP||Ph: (708) 327 3221|
|Joseph Clark, MD||Principal Investigator|
|Luther General Cancer Care Institute|
|Gina Kanevsky, MD, CRA, Primary Study Coord.||Ph: 847-410-0660|
|Sigrun Hallmeyer||Principal Investigator|
|Indiana University Melvin and Bren Simon Cancer Center|
|Michele Niland, RN, BSN, OCN||Ph: 317-278-0778|
|Theodore Logan, MD||Principal Investigator|
|Holden Comprehensive Cancer Center at University of Iowa|
|Melanie Frees, RN||Ph: 319-356-1228|
|Mohammed Milhem||Principal Investigator|
|Evie Key, RN, BSN, BA||Ph: 225-767-0822|
|Gerald Miletello, MD||Principal Investigator|
|University of Michigan Comprehensive Cancer Center|
|Susan Patton, RN||Ph: 734-936-8773|
|Christopher D. Lao, MD, MPA||Principal Investigator|
|Barbara Ann Karmanos Cancer Institute|
|Lawrence Flaherty, MD||Ph: 313-576-8725|
|Contact Person||Ph: 800-527-6266|
|Lawrence Flaherty, MD||Principal Investigator|
|Masonic Cancer Center at University of Minnesota|
|Carrie McCann, RN||Ph: 612-626-2569|
|Venkatesh Rudrapatna, MD, MPH||Principal Investigator|
|Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center|
|Eryn Bagley||Ph: 603-650-4035|
|Marc Stuart Ernstoff||Principal Investigator|
|Hackensack University Medical Center Cancer Center|
|Danielle Blair, RN, BSN, OCN||Ph: 551-996-5809|
|Robert Alter, MD||Principal Investigator|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center|
|Amiya R. Vaz||Ph: 212-305-1317|
|Bret Taback, MD||Principal Investigator|
|Christ Hospital Cancer Center|
|Pam Manfresca, RN, BSN, OCN||Ph: 513-585-0844|
|Philip Leming, MD||Principal Investigator|
|Case Comprehensive Cancer Center|
|Donna Prots, RN||Ph: 216-844-5393|
|Henry Koon, MD||Principal Investigator|
|Providence Cancer Center at Providence Portland Medical Center|
|Chris Fountain, RN, OCN||Ph: 503-215-2691|
|Brendan D. Curti||Principal Investigator|
|Saint Luke's Hospital - Anderson Campus|
|Rose Cabral||Ph: 484-503-4151|
|Tracy Max, MS, CCRP||Ph: 484-526-5190|
|Sanjiv S. Agarwala||Principal Investigator|
|UPMC Cancer Centers|
|Mollie Maguire, RN, BSN||Ph: 412-623-4004|
|John Munn Kirkwood||Principal Investigator|
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01683188
ClinicalTrials.gov processed this data on March 13, 2014
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