Ipilimumab With or Without High-Dose Recombinant Interferon Alfa-2b in Treating Patients With Stage III-IV Melanoma That Cannot Be Removed by Surgery
Recurrent Melanoma, Stage IIIA Cutaneous Melanoma AJCC v7, Stage IIIB Cutaneous Melanoma AJCC v7
About this trial
This is an interventional treatment trial for Recurrent Melanoma
Eligibility Criteria
Inclusion Criteria:
- Patients must have unresectable stage III or stage IV melanoma, either initial presentation or recurrent, that is of cutaneous origin or unknown primary origin and that is histologically diagnosed
- No more than one prior systemic therapeutic regimen for unresectable stage III or stage IV melanoma; this includes chemotherapy, biologic therapy, biochemotherapy, or investigational treatment; this does not include any therapies given in the adjuvant setting; however, patients are excluded if they have a history of prior treatment for melanoma (either adjuvant or metastatic disease) with ipilimumab or other cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, or prior interferon-alpha treatment for metastatic disease (history of adjuvant interferon-alpha is allowed); there should be a 4-week washout period between last treatment administration and initiation of study therapy
- Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Patients must not have other significant medical, surgical, or psychiatric conditions or require any medication or treatment that in the opinion of the investigator may interfere with compliance, make the administration of ipilimumab or HDI hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea; patients must not have an active infection requiring current treatment with parenteral antibiotics
- Patients must not have a history of inflammatory bowel disease or diverticulitis (history of diverticulosis is allowed)
Patients who have other current malignancies are not eligible; patients with other malignancies are eligible if they have been continuously disease free for > 5 years prior to the time of randomization; one exception are patients treated with a curative intent and are continuously disease free for > 3 years; these patients would be considered eligible:
- Patients with prior history at any time of any in situ cancer, lobular carcinoma of the breast in situ, cervical cancer in situ, atypical melanocytic hyperplasia or Clark I melanoma in situ are eligible
- Patients with prior history of basal or squamous skin cancer are eligible
- Patients must not have autoimmune disorders or conditions of immunosuppression that require current ongoing treatment with systemic corticosteroids (or other systemic immunosuppressants), including oral steroids (e.g., prednisone, dexamethasone) or continuous use of topical steroid creams or ointments or ophthalmologic steroids; a history of occasional (but not continuous) use of steroid inhalers is allowed; replacement doses of steroids for patients with adrenal insufficiency are allowed; patients who discontinue use of these classes of medication for at least 2 weeks prior to randomization are eligible if, in the judgment of the treating physician investigator, the patient is not likely to require resumption of treatment with these classes of drugs during the study; exclusion from this study also includes patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, Sjogren's syndrome, autoimmune vasculitis [e.g., Wegener's granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and Myasthenia gravis); other central nervous system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis); patients with autoimmune hypothyroid disease or type I diabetes on replacement treatment are eligible
- Due to the possible effect of treatment with ipilimumab on the immunologic response to infectious disease vaccines, patients must not have had any infectious disease vaccination (e.g, standard influenza, H1N1 influenza, pneumococcal, meningococcal, tetanus toxoid) within 4 weeks prior to randomization
Women must not be pregnant or breast-feeding; all females of childbearing potential must have a blood test or urine study during screening to rule out pregnancy; NOTE: a woman of childbearing potential (WOCBP) is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); for the purposes of this study, post-menopause is defined as:
- Amenorrhea >= 24 consecutive months without another cause, or
- For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (e.g., vasectomy) should be considered to be of childbearing potential; men of fathering potential and WOCBP must be using an adequate method of contraception or must abstain from sexual intercourse to avoid conception/pregnancy throughout the study and for up to 26 weeks after the last dose of ipilimumab or HDI in such a manner that the risk of pregnancy is minimized; men or WOCBP who are unwilling or unable to strictly follow this requirement are not eligible
- White blood cells (WBC) >= 3000/uL
- Absolute neutrophil count (ANC) >= 1500/uL
- Platelets >= 100 x 10^3/uL
- Hemoglobin >= 10 g/dL
- Serum creatinine =< 1.8 mg/dl
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x upper limit of normal (ULN) for patients with liver metastases and =< 2.0 x ULN for patients without liver metastases
- Serum bilirubin < 2 x ULN for patients with liver metastases and =< 1.5 x ULN for patients without liver metastases, (except patients with Gilbert's syndrome, who must have a total bilirubin < 3.0 mg/dL)
- No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- Patients must be free of brain metastasis by contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) scans within 4 weeks prior to enrollment; if known to have prior brain metastases, must not have evidence of active brain disease after definitive therapy (surgery, radiation therapy or stereotactic radiosurgery) on two successive MRI evaluations at least 3 months apart (one of which is =< 4 weeks prior to starting the study drugs)
- All sites of disease must be evaluated within 4 weeks prior to randomization; patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
Sites / Locations
- University of Alabama at Birmingham Cancer Center
- Rocky Mountain Cancer Centers-Aurora
- The Medical Center of Aurora
- Boulder Community Hospital
- Rocky Mountain Cancer Centers-Boulder
- Penrose-Saint Francis Healthcare
- Rocky Mountain Cancer Centers-Penrose
- Porter Adventist Hospital
- Colorado Blood Cancer Institute
- Presbyterian - Saint Lukes Medical Center - Health One
- SCL Health Saint Joseph Hospital
- Rose Medical Center
- Western States Cancer Research NCORP
- Mountain Blue Cancer Care Center - Swedish
- Swedish Medical Center
- North Colorado Medical Center
- Saint Anthony Hospital
- Rocky Mountain Cancer Centers-Littleton
- Littleton Adventist Hospital
- Sky Ridge Medical Center
- Longmont United Hospital
- McKee Medical Center
- Parker Adventist Hospital
- Rocky Mountain Cancer Centers-Parker
- Saint Mary Corwin Medical Center
- SCL Health Lutheran Medical Center
- Smilow Cancer Hospital Care Center at Saint Francis
- Beebe Medical Center
- Christiana Gynecologic Oncology LLC
- Delaware Clinical and Laboratory Physicians PA
- Helen F Graham Cancer Center
- Medical Oncology Hematology Consultants PA
- Christiana Care Health System-Christiana Hospital
- Beebe Health Campus
- TidalHealth Nanticoke / Allen Cancer Center
- Christiana Care Health System-Wilmington Hospital
- Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
- Saint Alphonsus Cancer Care Center-Boise
- Rush - Copley Medical Center
- Saint Joseph Medical Center
- Illinois CancerCare-Bloomington
- Illinois CancerCare-Canton
- Illinois CancerCare-Carthage
- Centralia Oncology Clinic
- Northwestern University
- Carle at The Riverfront
- Cancer Care Specialists of Illinois - Decatur
- Decatur Memorial Hospital
- Heartland Cancer Research NCORP
- Carle Physician Group-Effingham
- Crossroads Cancer Center
- Illinois CancerCare-Eureka
- Illinois CancerCare-Galesburg
- Western Illinois Cancer Treatment Center
- Ingalls Memorial Hospital
- Hematology Oncology Associates of Illinois-Highland Park
- AMG Libertyville - Oncology
- Illinois CancerCare-Macomb
- Carle Physician Group-Mattoon/Charleston
- Garneau, Stewart C MD (UIA Investigator)
- Porubcin, Michael MD (UIA Investigator)
- Spector, David MD (UIA Investigator)
- Trinity Medical Center
- Illinois CancerCare-Monmouth
- Illinois Cancer Specialists-Niles
- Carle Cancer Institute Normal
- Cancer Care Center of O'Fallon
- Illinois CancerCare-Ottawa Clinic
- Ottawa Regional Hospital and Healthcare Center
- Illinois CancerCare-Pekin
- OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
- Proctor Hospital
- Illinois CancerCare-Peoria
- OSF Saint Francis Radiation Oncology at Peoria Cancer Center
- Methodist Medical Center of Illinois
- OSF Saint Francis Medical Center
- Illinois CancerCare-Peru
- Valley Radiation Oncology
- Swedish American Hospital
- SwedishAmerican Regional Cancer Center/ACT
- Hematology Oncology Associates of Illinois - Skokie
- Central Illinois Hematology Oncology Center
- Southern Illinois University School of Medicine
- Springfield Clinic
- Memorial Medical Center
- Carle Cancer Center
- The Carle Foundation Hospital
- Rush-Copley Healthcare Center
- IU Health Central Indiana Cancer Centers-East
- Franciscan Saint Anthony Health-Michigan City
- Woodland Cancer Care Center
- Mary Greeley Medical Center
- McFarland Clinic - Ames
- Constantinou, Costas L MD (UIA Investigator)
- McFarland Clinic - Boone
- Medical Oncology and Hematology Associates-West Des Moines
- Iowa Methodist Medical Center
- Iowa-Wide Oncology Research Coalition NCORP
- Medical Oncology and Hematology Associates-Des Moines
- Mission Cancer and Blood - Laurel
- Iowa Lutheran Hospital
- McFarland Clinic - Trinity Cancer Center
- McFarland Clinic - Jefferson
- McFarland Clinic - Marshalltown
- Siouxland Regional Cancer Center
- Mercy Medical Center-Sioux City
- Saint Luke's Regional Medical Center
- Methodist West Hospital
- Cancer Center of Kansas - Chanute
- Cancer Center of Kansas - Dodge City
- Cancer Center of Kansas - El Dorado
- Cancer Center of Kansas - Fort Scott
- Cancer Center of Kansas-Independence
- Cancer Center of Kansas-Kingman
- Lawrence Memorial Hospital
- Cancer Center of Kansas-Liberal
- Cancer Center of Kansas-Manhattan
- Cancer Center of Kansas - McPherson
- Cancer Center of Kansas - Newton
- Cancer Center of Kansas - Parsons
- Cancer Center of Kansas - Pratt
- Cancer Center of Kansas - Salina
- Cancer Center of Kansas - Wellington
- Associates In Womens Health
- Cancer Center of Kansas-Wichita Medical Arts Tower
- Ascension Via Christi Hospitals Wichita
- Cancer Center of Kansas - Wichita
- Wichita NCI Community Oncology Research Program
- Cancer Center of Kansas - Winfield
- Ochsner Health Center-Summa
- Ochsner Baptist Medical Center
- Ochsner Medical Center Jefferson
- Greater Baltimore Medical Center
- Christiana Care - Union Hospital
- Bixby Medical Center
- Hickman Cancer Center
- Michigan Cancer Research Consortium NCORP
- Saint Joseph Mercy Hospital
- Beaumont Hospital - Dearborn
- Ascension Saint John Hospital
- Green Bay Oncology - Escanaba
- Genesys Hurley Cancer Institute
- Hurley Medical Center
- Green Bay Oncology - Iron Mountain
- Allegiance Health
- Sparrow Hospital
- Trinity Health Saint Mary Mercy Livonia Hospital
- Mercy Memorial Hospital
- Toledo Clinic Cancer Centers-Monroe
- Lake Huron Medical Center
- Ascension Saint Mary's Hospital
- Fairview Ridges Hospital
- Mercy Hospital
- Fairview Southdale Hospital
- Unity Hospital
- Hutchinson Area Health Care
- Minnesota Oncology Hematology PA-Maplewood
- Saint John's Hospital - Healtheast
- Abbott-Northwestern Hospital
- Hennepin County Medical Center
- Health Partners Inc
- New Ulm Medical Center
- North Memorial Medical Health Center
- Metro Minnesota Community Oncology Research Consortium
- Park Nicollet Clinic - Saint Louis Park
- Regions Hospital
- United Hospital
- Saint Francis Regional Medical Center
- Lakeview Hospital
- Ridgeview Medical Center
- Rice Memorial Hospital
- Minnesota Oncology Hematology PA-Woodbury
- Parkland Health Center-Bonne Terre
- Saint Francis Medical Center
- Southeast Cancer Center
- Capital Region Southwest Campus
- Missouri Baptist Medical Center
- Sainte Genevieve County Memorial Hospital
- Missouri Baptist Sullivan Hospital
- Missouri Baptist Outpatient Center-Sunset Hills
- Nebraska Hematology and Oncology
- Nebraska Cancer Research Center
- Southeast Nebraska Cancer Center - 68th Street Place
- Missouri Valley Cancer Consortium
- Alegent Health Immanuel Medical Center
- Alegent Health Bergan Mercy Medical Center
- Nebraska Cancer Specialists - Omaha
- Alegent Health Lakeside Hospital
- Oncology Hematology West PC
- Creighton University Medical Center
- Regional West Medical Center Cancer Center
- Cooper Hospital University Medical Center
- Veterans Adminstration New Jersey Health Care System
- Hunterdon Medical Center
- Rutgers Cancer Institute of New Jersey
- New York Oncology Hematology PC - Albany Medical Center
- Stony Brook University Medical Center
- Summa Health System - Akron Campus
- Strecker Cancer Center-Belpre
- Toledo Clinic Cancer Centers-Bowling Green
- Adena Regional Medical Center
- MetroHealth Medical Center
- Columbus Oncology and Hematology Associates Inc
- Riverside Methodist Hospital
- Columbus NCI Community Oncology Research Program
- Grant Medical Center
- The Mark H Zangmeister Center
- Mount Carmel Health Center West
- Doctors Hospital
- Delaware Health Center-Grady Cancer Center
- Delaware Radiation Oncology
- Grady Memorial Hospital
- Fairfield Medical Center
- Lancaster Radiation Oncology
- Lima Memorial Hospital
- Marietta Memorial Hospital
- Toledo Clinic Cancer Centers-Maumee
- Knox Community Hospital
- Licking Memorial Hospital
- Newark Radiation Oncology
- Saint Charles Hospital
- Toledo Clinic Cancer Centers-Oregon
- Southern Ohio Medical Center
- Springfield Regional Medical Center
- ProMedica Flower Hospital
- Mercy Hospital of Tiffin
- ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital
- Saint Vincent Mercy Medical Center
- University of Toledo
- Toledo Community Hospital Oncology Program CCOP
- Mercy Health - Saint Anne Hospital
- Toledo Clinic Cancer Centers-Toledo
- Fulton County Health Center
- Saint Ann's Hospital
- Genesis Healthcare System Cancer Care Center
- Natalie Warren Bryant Cancer Center at Saint Francis
- Geisinger Medical Center
- Geisinger Medical Center-Cancer Center Hazleton
- Geisinger Medical Oncology-Lewisburg
- Lewistown Hospital
- Fox Chase Cancer Center
- University of Pittsburgh Cancer Institute (UPCI)
- Geisinger Cancer Services-Pottsville
- Geisinger Medical Group
- Geisinger Wyoming Valley/Henry Cancer Center
- Erlanger Medical Center
- Fredericksburg Oncology Inc
- West Virginia University Charleston Division
- Aurora Cancer Care-Southern Lakes VLCC
- Aurora Health Center-Fond du Lac
- Aurora Health Care Germantown Health Center
- Aurora Cancer Care-Grafton
- Green Bay Oncology at Saint Vincent Hospital
- Saint Vincent Hospital Cancer Center Green Bay
- Green Bay Oncology Limited at Saint Mary's Hospital
- Saint Vincent Hospital Cancer Center at Saint Mary's
- Aurora BayCare Medical Center
- UW Cancer Center Johnson Creek
- Aurora Cancer Care-Kenosha South
- Gundersen Lutheran Medical Center
- University of Wisconsin Carbone Cancer Center
- Holy Family Memorial Hospital
- Aurora Bay Area Medical Group-Marinette
- Bay Area Medical Center
- Aurora Cancer Care-Milwaukee
- Ascension Southeast Wisconsin Hospital - Saint Joseph Campus
- Aurora Saint Luke's Medical Center
- Medical College of Wisconsin
- Aurora Sinai Medical Center
- Cancer Center of Western Wisconsin
- Saint Vincent Hospital Cancer Center at Oconto Falls
- Vince Lombardi Cancer Clinic - Oshkosh
- Aurora Cancer Care-Racine
- HSHS Saint Nicholas Hospital
- Vince Lombardi Cancer Clinic-Sheboygan
- Green Bay Oncology - Sturgeon Bay
- Aurora Medical Center in Summit
- Vince Lombardi Cancer Clinic-Two Rivers
- Aurora Cancer Care-Waukesha
- Aurora Cancer Care-Milwaukee West
- Aurora West Allis Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Arm A (higher dose ipilimumab, HDI)
Arm B (higher dose ipilimumab)
Arm C (lower dose ipilimumab + HDI)
Arm D (lower dose ipilimumab)
INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.
INDUCTION PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive higher dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.
INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses and recombinant interferon alfa-2b IV over 20 minutes 5 days a week for 4 weeks and then SC 3 times weekly for 8 weeks. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24 and recombinant interferon alfa-2b SC 3 times weekly for 48 weeks.
INDUCTION PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 3 weeks for 4 doses. MAINTENANCE PHASE: Patients receive lower dose ipilimumab IV over 90 minutes once every 12 weeks for 4 doses beginning in week 24.