E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 evaluate the Best Overall Response Rate (BORR), (as per modified WHO criteria) in patients with previously treated Stage III (unresectable) or Stage IV melanoma receiving ipilimumab. |
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E.2.2 | Secondary objectives of the trial |
1) To estimate disease control rate (proportion of patients with best response of complete response [CR] + partial response [PR] + stable disease [SD]); 2) To estimate progression free survival (PFS) rate at Week 12; 3) To estimate PFS; 4) To estimate overall survival (OS); 5) To estimate survival rate at one year; 6) To estimate duration of best overall response (BOR) and to evaluate the proportion of patients whose duration of response is ≥ 24 weeks; 7) To estimate time to BOR; 8) To evaluate the safety profile of ipilimumab during the Induction and Maintenance Phases; 9) To evaluate health-related quality of life (HRQoL); 10) To obtain pharmacokinetic (PK) samples for population PK analysis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Willing and able to give written informed consent; 2) Histologic diagnosis of malignant melanoma; 3) Measurable melanoma, as per modified WHO criteria; 4) Stage III (unresectable) or Stage IV melanoma; 5) Patient must have progressed during or after at least one prior therapeutic regimen containing at least one of the following: IL-2, dacarbazine, paclitaxel, carboplatin, fotemustine, or temozolamide. 6) Have a full set of baseline (i.e., Screening) digital images of cutaneous lesions and radiographic images, including, but not limited to: brain, bone, chest, abdomen and pelvis. All images must be of adequate quality as detailed in Section 3.3.1 of the protocol. 7) Life expectancy ≥ 16 weeks; 8) ECOG performance status of 0 or 1 (see Protocol Appendix 4); 9) Required values for initial laboratory tests: • WBC ≥ 2500/uL • ANC ≥ 1000/uL • Platelets ≥ 75 x 103/uL • Hemoglobin ≥ 9 g/dL • Creatinine ≤ 2.5 x ULN • AST ≤ 3 x ULN for patients without liver metastasis / ≤ 5 x ULN for patients with liver metastasis • Bilirubin ≤ 3 x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/mL); 10) 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. 11) Male and female patients ≥ 16 years of age (or minimum age of consent required per given 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 period of the study and for up to 8 weeks after the study; 2) Women who are pregnant or breastfeeding; 3) Women with a positive pregnancy test at enrollment or prior to study drug administration; 4) Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control;
Target Disease Exceptions 5) Any 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, carcinoma in situ of the cervix; 6) Primary ocular or mucosal melanoma;
Medical History and Concurrent Disease 7) Evidence of brain metastases on brain MRI or contrast CT; 8) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Chrohn’s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (e.g. rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis] 9) Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea;
Prohibited Therapies and/or Medications 10) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of study drug); surgery or radiotherapy (except as described 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); 11) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; 12) Previous enrollment in another clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist;
Other Exclusion Criteria 13) Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled in 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 timepoints and as clinically indicated. For the purpose of final analysis of study results, an IRC will review all images from all timepoints 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 7.3.5.1. Ipilimumab 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 evaluated as described in 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 adverse event (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: Will be assessed as measured by the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC)
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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 | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 31 |
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 | Yes |
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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The end of the study will occur at the same time as the primary analysis. Any patients who remain on study at the end of the trial may be switched to a follow-up protocol to enable the current study to be closed and reported. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |