E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III, IV metastatic advanced melanoma |
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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 monitor the safety of ipilimumab (MDX-010) administered either as Re-Induction (10 mg/kg) or as Maintenance therapy (0.3, 3 or 10 mg/kg) in this ipilimumab (MDX-010) clinical study. |
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E.2.2 | Secondary objectives of the trial |
For all patients: 1)OS from 1st dose of ipilimumab in prior/parent study 2)survival rate at 1 year from 1st dose of ipilimumab in prior/parent study 3)monitor patients who experience IBEs after ipilimumab treatment
For patients receiving Re-Induction in this study at time of disease progression, following clinical benefit (SD, PR or CR) after ipilimumab treatment: 4)BORR following 1st Re-Induction in this study 5)Disease control rate following 1st Re-Induction in this study 6)Duration of BOR following 1st Re-Induction in this study 7)Time to BOR following 1st Re-Induction in this study 8)OS following 1st Re-Induction in this study 9)Repeat response following 2nd Re-Induction in this study
For all patients receiving Re-Induction or Maintenance treatment with ipilimumab in this study, estimate: 10)PFS from 1st Re-Induction in this study 11)continued PFS from 1st dose ipilimumab in prior/parent study 12)duration of BOR following 1st dose ipilimumab in prior/parent study |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients eligible for this study must represent one of the three patient populations described in Section 3.2 of the Protocol and meet the inclusion/exclusion criteria detailed below.
1. Willing and able to give written informed consent;
Target population 2. Diagnosis of advanced melanoma; 3. Prior treatment in one of the following studies: CA184008, CA184-022, CA184007, CA184004, MDX010-08 or MDX010-15; 4. Accessible for treatment and Follow-Up; 5. All patients entering the study as Group A to receive Re-Induction must have their case discussed with a BMS Medical Monitor prior to enrollment in the companion study; 6. Tolerating ipilimumab treatment (i.e., no unacceptable toxicity requiring study drug discontinuation - refer to Protocl Section 6.2.4); 7. Have the complete set of baseline (i.e., Screening) images of lesions and radiographic images, including, but not limited to: brain, chest, abdomen pelvis and bone scans (bone scan only as applicable). All images must be of adequate quality; 8. Life expectancy ≥16 weeks; 9. ECOG performance status of 0 or 1 (refer to Protocol Appendix 3); 10. Required values for initial laboratory tests: - WBC ≥ 2500/uL - ANC ≥ 1000/uL - Platelets ≥ 75 x 103/uL - Hemoglobin ≥ 9 g/dL - Creatinine ≤ 2.5x ULN - AST ≤ 3 x ULN for patients without liver metastasis; ≤ 5 x ULN for patients with liver metastasis - Bilirubin ≤ 3x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/mL); 11. 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 Medical Monitor;
Age and Sex 12. Men and women ≥18 years of age (or, ≥ 16, if allowable per local regulatory authority); 13. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
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E.4 | Principal exclusion criteria |
A/ For Group A, B and C patients:
1. Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist, except for ipilimumab; 2. Prisoners or patients who are compulsorily detained.
B/ For Group A and Group B patients:
Sex and Reproductive Status 3. 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; 4. Women who are pregnant or breastfeeding; 5. Women with a positive pregnancy test on enrollment or prior to study drug administration; 6. Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control;
Target Disease Exceptions 7. Primary ocular or mucosal melanoma;
Medical History and Concurrent Diseases 8. 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 9. Prior or concomitant therapy with any anti-cancer agent, immunosuppressive agents, surgery or radiotherapy (except as defined in Protocol Sections 6.2.8.3 and 6.2.8.4); and chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). 10. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab); 11. Treatment with other investigational products within the last 4 weeks prior to or during this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy Measures: The Investigator will make all tumor evaluations based on modified World Health Organization (WHO) criteria (Refer to Protocol Section 3.3.2). Throughout the study each respective Investigator will determine disease status of patients at the protocol-defined time points and as clinically indicated.
Safety Measures: Safety will be evaluated for all 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 either be: 1) from the date of the first dose of ipilimumab received in this study (Group A and B patients) to 70 days (5 half-lives) following the last dose received; or 2) 70 days from the last dose of ipilimumab received in the prior/parent study (Group C patients).
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 75 |
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 | No |
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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This study will continue to enroll new patients until/if ipilimumab becomes commercially available at all open sites or the Investigational New Drug Application (IND) is closed by the Sponsor. It will remain open until the last enrolled patient discontinues from any study Phase, including Follow-Up or the study is otherwise terminated by the Sponsor. |
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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 | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |