Adjuvant immunotherapy with anti-CTLA-4 monoclonal antibody (ipilimumab) versus placebo after complete resection of high-risk Stage III melanoma: A randomized, doubleblind Phase 3 trial of the EORTC Melanoma Group - EORTC protocol 18071
- Conditions
- High Risk Stage III melanomaMedDRA version: 9.1Level: LLTClassification code 10025670Term: Malignant melanoma stage III
- Registration Number
- EUCTR2007-001974-10-IT
- Lead Sponsor
- Bristol-Myers Squibb International
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1211
1) Signed Written Informed Consent - Written informed consent required prior to clinical trial participation, including informed consent for any screening procedures conducted to establish subject eligibility for the trial registration, according to ICH/EU GCP, and national/local regulations 2) Target Population - No mucosal or ocular melanoma, or melanoma with unknown origin of the primary - Complete resection of Stage III melanoma (AJCC R0) with histologically confirmed cutaneous melanoma metastatic to lymph node, classified as (AJCC, 2002): Stage IIIA with metastasis > 1mm; any Stage IIIB or IIIC (no in-transit metastases) - Adequate resection of Stage III lymph nodes per Criteria for adequate surgical procedures for complete lymph node dissection (CLND) as documented on the operating report and pathology report. Patients without documentation of adequate resection are not eligible - Recommendations for management of the lymph nodes are given in Appendix J and should include the following: a) Head and Neck - Minimum of 15 pathologically investigated nodes - Face, ear, and anterior scalp: parotidectomy plus modified radical neck dissection - Posterior scalp: modified radical neck dissection plus suboccipital nodes b) Upper Extremity - Minimum of 10 pathologically investigated nodes - Axillary node dissection included at least 10 nodes taken from Levels I and II - Level III nodes dissected if they were clinically involved - Pectoralis minor muscle was divided or sacrificed c) Lower Extremity - Minimum of 5 pathologically investigated nodes - Superficial inguinal node dissection was performed for non-palpable nodal involvement - If Cloquet?s node was positive, a deep inguinal node dissection was performed d) Lymph Node Dissection for Nodal Recurrence - Regional node recurrence was treated using the appropriate lymphadenectomy as above - Diagnosis of regional node recurrence was made by fine needle aspiration technique to avoid contaminating the region with tumor, followed by CLND as above - Full lymphadenectomy must be performed within 12 weeks (84 days) prior to randomization - Disease status for the post-surgery baseline assessment must be documented by full Chest/Abdomen/Pelvis CT and/or MRI with Neck CT and/or MRI (for Head and Neck primaries) and complete clinical examination after the informed consent and prior to randomization - The complete set of baseline radiographic images must be available before randomization and all images must be of adequate quality 3) Physical and Laboratory Test Findings - Disease-free (no loco-regional relapse or distant metastasis); no clinical evidence for brain metastases - ECOG performance status of 0 or 1 (see Appendix B) - Adequate cardiac function (less or equal to NYHA II, see Appendix C) - Adequate hematologic, renal and liver function as defined by laboratory values performed within 4-6 weeks from enrollment - White blood count (WBC) greater than or equal to 2.5x10 (9)/L - Absolute neutrophil count (ANC) greater than or equal to 1x10 (9)/L - Platelet count greater than or equal to 75x10 (9)/L - Hemoglobin greater than or equal to 9 g/dL (5.6 mmol/L) - Serum creatinine less or equal to 2.5 times upper limit of laboratory normal range (ULN) - Total serum bilirubin, AST, ALT, alkaline phosphatase and LDH less or equal to 2 times ULN 4) Age and Sex - At least 18 years of age - WOCBP (including women who are using oral implanted or injectable contraceptive hormones or mechanical products such as
1) Sex and Reproductive Status - WOCBP unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the last administration of the perfusion, women who are pregnant or breastfeeding, women with a positive pregnancy test on enrollment or prior to study drug administration, and sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control 2) Medical History and Concurrent Diseases - No radiation therapy to the lymph node dissection field after surgery - No prior therapy for melanoma except surgery for primary melanoma lesions; patients who have previously received IFN are not eligible - No prior or concomitant therapy with any anti-cancer agents, immunosuppressive agents; other investigational anti-cancer therapies, or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses) - No non-oncology vaccine therapy can be used for prevention of infectious diseases (up-to) 4 weeks prior and after any dose of ipilimumab or placebo - No prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist - No previous participation in another ipilimumab (MDX-010) clinical trial - No treatment with other investigational products within the last 4 weeks prior to randomization into this study - No uncontrolled infectious disease including negative testing for HIV, HBV, HCV - No autoimmune disease: patients with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn?s disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, autoimmune thyroiditis (e.g. Hashimoto?s disease), autoimmune hepatitis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis (e.g., Wegener?s Granulomatosis) - Patients must not present immunodeficiency or previous splenectomy or radiation therapy to the spleen - No second malignancies in the past 5 years with the exception of surgically cured carcinoma in-situ of the cervix and basal or squamous cell carcinoma of the skin 6) Other Exclusion Criteria - Patients must have absence of any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs or efficacy, such as a condition associated with frequent diarrhea - No prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must be randomized into this study - Patients must have absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method