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Clinical Trials (PDQ®)

Clinical Trials (PDQ®)

Ipilimumab or High-Dose Interferon Alfa-2b in Treating Patients With High-Risk Stage III-IV Melanoma That Has Been Removed by Surgery

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IIIBiomarker/Laboratory analysis, TreatmentActive18 and overNCINCI-2011-02649
CDR0000692568, ECOG-E1609, E1609, U10CA180820, U10CA021115, NCT01274338

Trial Description

Summary

This randomized phase III trial studies ipilimumab to see how well it works compared to high-dose interferon alfa-2b in treating patients with high-risk stage III-IV melanoma that has been removed by surgery. Monoclonal antibodies, such as ipilimumab, may interfere with the ability of tumor cells to grow and spread. Interferon alfa-2b may interfere with the growth of tumor cells and slow the growth of melanoma and other cancers. It is not yet known whether ipilimumab is more effective than interferon alfa-2b in treating patients with melanoma.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate recurrence-free survival (RFS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (high dose ipilimumab; HIP) or 3 mg/kg (low dose ipilimumab: LIP) versus those randomized to receive high-dose interferon alfa-2b (HDI) utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

II. To evaluate overall survival (OS) between patients randomized to receive post-operative adjuvant ipilimumab given at either 10 mg/kg (HIP) or 3 mg/kg (LIP) versus those randomized to receive HDI utilizing a hierarchical design assessing HIP versus HDI first and LIP versus HDI second (if the first comparison is significant).

SECONDARY OBJECTIVES:

I. To evaluate safety and tolerability of post-operative adjuvant ipilimumab therapy given at either 10 mg/kg (HIP) or 3 mg/kg (LIP).

II. Among patients enrolled by Clinical Community Oncology programs (CCOPs), to compare the global quality of life (QOL) between the ipilimumab arms versus HDI using Functional Assessment of Cancer Therapy (FACT)-General (G) form and to evaluate the effect of treatment-related side effects that may have an impact on the health-related domains of QOL using Functional Assessment of Chronic Illness Therapy (FACIT)-diarrhea (D) and FACT-biological response modifiers (BRM).

OUTLINE: Patients are age >= 18 are randomized to Arms A, B, or C and patients ages 12-17 are randomized to Arms D, E, or F.

ARM A: Patients receive induction high-dose ipilimumab intravenously (IV) over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity. (closed accrual as of 4/4/14)

ARM B: Patients receive induction high-dose recombinant interferon alfa-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

ARM D: Patients receive induction high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance high-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

ARM E: Patients receive induction high-dose recombinant interferon alfa-2b IV on days 1-5, 8-12, 15-19, and 22-26 in the absence of disease progression or unacceptable toxicity. Patients then receive maintenance high-dose recombinant interferon alfa-2b subcutaneously (SC) on days 1, 3, and 5. Treatment repeats every week for 48 weeks in the absence of disease progression or unacceptable toxicity

ARM F: Patients receive induction low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Beginning on week 24, patients receive maintenance low-dose ipilimumab IV over 90 minutes on day 1. Treatment repeats every 90 days for a maximum of 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for up to 15 years.

Eligibility Criteria

Inclusion Criteria:

  • All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization; imaging studies must include a total body positron emission tomography (PET)-computed tomography (CT) scan (with or without brain) and brain magnetic resonance imaging (MRI) or CT (if MRI is contraindicated); if PET-CT cannot be done, CT of neck, chest, abdomen, and pelvis should be done
  • If for some reason a CT cannot be done, an MRI may be done instead; any other imaging studies if performed (eg, bone scan) must show no evidence of disease
  • Patients must have primary cutaneous melanoma that belongs to one of the following American Join Commission on Cancer (AJCC) stages (2009 AJCC Melanoma Staging System):
  • Stage IIIB
  • T1-4b N1a M0
  • T1-4b N2a M0
  • T1-4b N1b M0
  • T1-4b N2b M0
  • T1-4b N2c M0
  • Stage IIIC
  • T1-4b N1b M0
  • T1-4b N2b M0
  • T1-4b N2c M0
  • Any T N3 M0
  • Stage IV
  • M1a
  • M1b
  • NOTE: patients with stage IV melanoma must have normal lactate dehydrogenase (LDH) and either distant skin, subcutaneous, lymph node, or lung metastases, but no other visceral metastases in order to be eligible; for patients with resected stage IV melanoma, LDH within the institutional upper limit of normal (ULN) must be documented within 4 weeks prior to randomization
  • Patients with disease recurrence after adequate surgical excision of the original primary cutaneous/unknown primary melanoma are allowed even if they don't fit the strict staging criteria, but only as follows:
  • Recurrence in a regional lymph node basin after a prior complete lymph node dissection; relapsed disease must be completely surgically resected with free margins
  • Recurrence in the form of in-transit or satellite metastases or distant skin/subcutaneous, nodal, or lung metastases that are completely surgically resected with free margins
  • Recurrence in a regional lymph node basin; relapsed disease must be completely surgically resected with free margins
  • Patients with unknown primary melanoma (Tx) who present with cutaneous, subcutaneous, nodal and/or lung metastases that are completely surgically resected with free margins are allowed; these patients are allowed even if they don't fit the strict staging criteria; for stage IV patients LDH within the institutional ULN must be documented within 4 weeks prior to randomization (M1c is not eligible)
  • NOTE: all subjects should be classified as IIIB, IIIC, M1a or M1b including subjects with disease recurrence after adequate surgical excision of the original primary melanoma; that is the treating team/physician investigator should review an overall TNM status (that includes primary tumor presentation and disease recurrence status) and provide a designation of IIIB, IIIC, M1a or M1b
  • Patients must be randomized within 84 days (12 weeks) of surgical resection; if more than one surgical procedure is required to render the patient disease-free, the patient must be randomized within 12 weeks of the last surgery
  • NOTE: patients with clinically positive lymph nodes for melanoma involvement or those with positive lymph nodes identified through lymphoscintigraphic and/or dye lymphographic techniques in the groin, axilla, or neck should have additional lymphadenectomy in those sites; the complete lymph node dissection procedure would be considered as the last surgery in counting the 84 days unless a subsequent surgical procedure(s) was clinically required to ensure the disease free status
  • Patients must not have received any adjuvant treatment (chemotherapy, biotherapy, or limb perfusion) after the resection(s) that make(s) them eligible for this trial
  • NOTE: previous radiation therapy, including after the surgical resection, is allowed as long as 21 days have elapsed between the radiation and initiation of this adjuvant systemic therapy
  • Prior treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior clusters of differentiation (CD)137 agonist or prior interferon-alfa is not allowed; other forms of prior treatment for melanoma (e.g., aldesleukin [IL-2], anti-tumor vaccine, chemotherapy) are allowed if given before the resection(s) that make(s) the patient eligible for this trial, but these must have been completed at least 4 weeks prior to randomization
  • Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Patients must not have an active infection requiring current treatment with parenteral antibiotics
  • 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 with a baseline of frequent diarrhea (e.g. irritable bowel syndrome) are not eligible
  • Patients should be carefully screened for depression at baseline and if there are indications or a history of depression it is strongly recommended that these patients be closely followed together with behavioral health or psychiatric medical support; patients with an established diagnosis of depression that, in the assessment of the investigator may make the administration of interferon (IFN)-alfa or ipilimumab hazardous, should not be enrolled on this protocol; the risks and benefits of being treated with standard adjuvant IFN-alfa should be weighed very carefully in consultation with behavioral health or psychiatry
  • Patients must not have a documented history of inflammatory bowel disease (including ulcerative colitis and Crohn's disease) or diverticulitis (history of diverticulosis is allowed)
  • 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 (i.e., 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, Sjögren'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
  • Patients must not have had any infectious disease vaccination (e.g., standard influenza, H1N1 influenza, pneumococcal, meningococcal, or tetanus toxoid) within 4 weeks prior to randomization
  • Patients must not be prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
  • 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; 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 melanoma in situ are eligible; patients with prior history of basal or squamous skin cancer are eligible; patients who have had multiple primary melanomas are eligible
  • 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: 1) 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); post-menopause is defined as:
  • Amenorrhea >= 12 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
  • WOCBP must be using an adequate method of contraception to avoid 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; 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 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
  • WOCBP are not eligible if they satisfy any of the following:
  • A positive pregnancy test at baseline
  • Pregnant or breastfeeding
  • White blood cell (WBC) >= 3,000/uL
  • Absolute neutrophil count (ANC) >= 1,500/uL
  • Platelets >= 100 x 10^3/uL
  • Hemoglobin >= 10 g/dL
  • Serum creatinine =< 1.5 mg/dL
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Serum bilirubin =< 1.5 x ULN, (except patients with Gilbert's syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; patients must have negative testing for HIV, hepatitis B virus (HBV), hepatitis C virus (HCV) within 4 weeks prior to randomization

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Ahmad TarhiniPrincipal Investigator

Trial Sites

U.S.A.
California
  Palo Alto
 Palo Alto Medical Foundation - Palo Alto
 David S Leibowitz Ph: 415-209-2686
  Email: bernicl@sutterhealth.org
  Santa Cruz
 Palo Alto Medical Foundation-Santa Cruz
 Glenn D Wong Ph: 415-209-2686
  Email: bernicl@sutterhealth.org
  Sunnyvale
 Palo Atlo Medical Foundation-Sunnyvale
 Peter P. Yu Ph: 415-209-2686
  Email: bernicl@sutterhealth.org
Connecticut
  Norwich
 Eastern Connecticut Hematology and Oncology Associates
 Dennis E. Slater Ph: 860-886-8362
Florida
  Stuart
 Robert and Carol Weissman Cancer Center at Martin Memorial
 Guillermo Abesada-Terk Ph: 772-288-5858ext4
 Guillermo Abesada-Terk Ph: 772-288-5858ext4
 Guillermo Abesada-Terk Ph: 772-288-5858ext4
Georgia
  Atlanta
 CCOP - Atlanta Regional
 Thomas E. Seay Ph: 404-303-3355
  Columbus
 John B. Amos Cancer Center
 Thomas E. Seay Ph: 404-303-3355
Illinois
  Galesburg
 Medical and Surgical Specialists, LLC
 Nguyet A Le-Lindqwister Ph: 800-793-2262
  Maywood
 Cardinal Bernardin Cancer Center at Loyola University Medical Center
 Joseph I. Clark Ph: 708-226-4357
  Oak Lawn
 Advocate Christ Medical Center
 Adam I Riker Ph: 800-323-8622
  Urbana
 Carle Cancer Center at Carle Foundation Hospital
 Adam I Riker Ph: 800-323-8622
Kansas
  Shawnee Mission
 Kansas City Cancer Center - Shawnee Mission
 Peter J. VanVeldhuizen Ph: 800-525-1483
Michigan
  Ann Arbor
 University of Michigan Comprehensive Cancer Center
 Ahmad A. Tarhini Ph: 412-647-8073
  Email: tarhiniaa@upmc.edu
New York
  Glens Falls
 Charles R. Wood Cancer Center at Glens Falls Hospital
 John P Stoutenburg Ph: 518-926-6700
North Carolina
  Kinston
 Kinston Medical Specialists
 Peter R. Watson Ph: 252-559-2200
  Rutherfordton
 Rutherford Hospital
 Charles E Bowers Ph: 800-486-5941
North Dakota
  Bismarck
 Bismarck Cancer Center
 Edward J. Wos Ph: 701-323-5760
  Email: tfischer@mohs.org
Ohio
  Canton
 Aultman Cancer Center at Aultman Hospital
 Kisa E Weeman Ph: 330-363-6891
  Cincinnati
 Christ Hospital Cancer Center
 Philip D. Leming Ph: 513-585-2859
Oklahoma
  Oklahoma City
 Oklahoma University Cancer Institute
 Alexandra P Ikeguchi Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
  Tulsa
 Cancer Care Associates-Yale
 Alexandra P Ikeguchi Ph: 405-271-4272
  Email: julie-traylor@ouhsc.edu
Pennsylvania
  West Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Terrence P. Cescon Ph: 610-988-9323
South Carolina
  Anderson
 AnMed Cancer Center
 Charles E Bowers Ph: 800-486-5941
West Virginia
  Charleston
 West Virginia University Medical School - Charleston
 Steven J. Jubelirer Ph: 304-344-3457
  Huntington
 Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
 Maria-Rosalia B. Tria Tirona Ph: 304-399-6617
Wisconsin
  La Crosse
 Gundersen Lutheran Center for Cancer and Blood
 Kurt Oettel Ph: 608-775-2385
  Email: cancerctr@gundluth.org
  Milwaukee
 Oncology Alliance, SC - Milwaukee - South
 Rubina Qamar Ph: 888-709-2080
 Wheaton Franciscan Cancer Care - St. Joseph
 Jonathan S. Treisman Ph: 414-427-2360

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01274338
ClinicalTrials.gov processed this data on October 19, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.