E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Untreated stage III unresectable or IV melanoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027156 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare PFS in patients with previously untreated Stage IIIc, N3 unresectable or Stage IV melanoma receiving dacarbazine plus 10mg/kg ipilimumab MDX-010 vs. dacarbazine with placebo. |
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E.2.2 | Secondary objectives of the trial |
To compare overall survival OS between two arms; 2 To estimate survival rate at 1 year for each treatment arm; 3 To compare PFS rate at Week 12 between two arms; 4 To compare best overall response rate BORR between two arms; 5 To estimate duration of best overall response BOR and the proportion of patients with duration of response lasting 8805; 24 weeks for each treatment arm; 6 To compare disease control rate proportion with best response of complete response CR partial response PR stable disease SD between two arms; 7 To estimate time to BOR for each treatment arm; 8 To evaluate the safety profile for each treatment arm; 9 To evaluate Health Related Quality of Life HRQoL for each treatment arm; 10 To obtain serum samples for population pharmacokinetics PK . |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Signed written informed consent 1 Willing and able to give written informed consent; Target population 2 Histologic diagnosis of malignant melanoma; 3 Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or in-transit/satellite metastases or Stage IV melanoma AJCC 2001 note that prior adjuvant melanoma therapy is permitted e.g., IFN therapy ; 4 Measurable/evaluable disease as per modified WHO criteria , within 28 days of first dose of study drug; 5 Life expectancy of 8805; 16 weeks; 6 ECOG performance status of 0 or 1 see Appendix 3 ; 7 Have the complete set of baseline i.e., Screening digital images of lesions and radiographic images, including, but not limited to brain, chest, abdomen pelvis and bone scans. All images must be of adequate quality; 8 Required values for initial laboratory tests WBC 8805; 2500/uL ANC 8805; 1000/uL Platelets 8805; 75 x 103/uL Hemoglobin 8805; 9 g/dL Creatinine 8804; 2.5x ULN AST 8804; 3 x ULN for patients without liver metastasis 8804; 5 x ULN for patients with liver metastasis Bilirubin 8804; 3x ULN, except patients with Gilbert s Syndrome, who must have a total bilirubin less than 3.0 mg/dL; 9 Negative Screening tests for HIV, HepB, and HepC. If positive results are not indicative of true active or chronic infection, the patient can enter the study after discussion and agreement between the Investigator and the CRO Medical Monitor; 10 Accessible for treatment and Follow-Up; Age and Sex 11 Men and women 18 years of age or, 8805; 16, if allowable per local regulatory authority . |
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E.4 | Principal exclusion criteria |
Sex and Reproductive Status 1 WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study. 2 Women who are pregnant or breastfeeding 3 Women with a positive pregnancy test on enrollment or prior to study drug administration. 4 Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control Medical History and Concurrent Diseases 5 Evidence of brain metastases on brain imaging i.e., MRI or contrast CT ; 6 Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix; 7 Primary ocular or mucosal melanoma; 8 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, systemic progressive sclerosis scleroderma , Systemic Lupus Erythematosus, autoimmune vasculitis e.g., Wegener s Granulomatosis ; 9 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, such as a condition associated with frequent diarrhea; Prohibited Therapies and/or Medications 10 Prior or concomitant therapy with any anti-cancer agent, immunosuppressive agents, surgery or radiotherapy except as defined in Sections 6.2.8.3 and 6.2.8.4 ; other investigational anti-cancer therapies, or chronic use of systemic corticosteroids used in the management of cancer or non-cancer-related illnesses . Prior adjuvant therapy is not exclusionary; 11 Any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks prior to or after any dose of ipilimumab or dacarbazine ; 12 Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist; 13 Previous participation in another ipilimumab MDX-010 clinical trial; 14 Treatment with other investigational products within the last 4 weeks prior to randomization into this study; |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Measures Investigator and Independent Review Committee IRC tumor evaluations will be based on modified WHO criteria. Throughout the study each respective Investigator will determine disease status of patients at the defined time points and as clinically indicated. For the purpose of final analysis of study results, an IRC will review all images from all time points for all patients and assess response parameters as specified. Pharmacokinetics Blood draws to assess the serum PK of ipilimumab will be drawn at the time points listed in Table 7.2.5.1. Serum concentration data will be used in conjunction with samples from other studies as part of the population PK assessment. Serum Human Anti-Human Antibodies HAHA will be collected as per Table 7.3.5.1. Safety Measures Safety will be evaluated for all treated patients using the National Cancer Institute NCI Common Terminology Criteria for Adverse Events v3.0 CTCAE . Safety assessments will be based on medical review of AE reports and the results of vital sign measurements, physical examinations and clinical laboratory tests. The incidence of AEs will be tabulated and reviewed for potential significance and clinical importance. The reporting period for safety data will be from the date of first on-study dose to 70 days 5 half-lives after the last dose is received. Health-related quality of life HRQoL will be assessed as measured by the European Organization for Research and Treatment of Cancer Quality of Life questionnaire EORTC and will be administered at multiple time-points throughout the study. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |