E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage III, IV metastatic advanced melanoma |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027156 |
E.1.2 | Term | Skin melanomas (excl ocular) |
|
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 administered either as Re-Induction (10 mg/kg)
or as Maintenance therapy (0.3, 3 or 10 mg/kg) in this ipilimumab clinical study. |
|
E.2.2 | Secondary objectives of the trial |
For all enrolled patients:
1) To estimate overall survival (OS) from the first dose of ipilimumab in the prior/parent study;
2) To estimate survival rate at 1 year from the first dose of ipilimumab in the prior/parent study;
3) To monitor patients who experience Immune Breakthrough Events (IBEs) after ipilimumab treatment.
For patients who receive Re-Induction in this study at the time of disease progression, following
clinical benefit (SD, PR or CR) after ipilimumab treatment:
4) Best objective response rate (BORR) following first Re-Induction in this study;
5) Disease control rate (proportion of patients with stable disease [SD], partial response [PR] or complete
response [CR]) following first Re-Induction in this study;
6) Duration of best objective response (BOR) following first Re-Induction in this study;
7) Time to BOR following first Re-Induction in this study;
8) To estimate OS following first Re-Induction in this study; |
|
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. 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 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 Appendix 3);
10. Required values for initial laboratory tests:
ユ WBC >= 2500/uL
ユ ANC >= 1000/uL
ユ Platelets >= 75 x 103/uL
ユ Hemoglobin >= 9 g/dL
ユ Creatinine <= 2.5x ULN
ユ AST <= 3 x ULN for patients without liver metastasis
<= 5 x ULN for patients with liver metastasis
ユ Bilirubin <= 3x ULN, (except patients with Gilbertメ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. |
|
E.4 | Principal exclusion criteria |
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 (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious disease) illness must not
be enrolled in this study.
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 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To monitor the safety of ipilimumab administered either as Re-Induction (10 mg/kg)
or as Maintenance therapy (0.3, 3 or 10 mg/kg) in this ipilimumab clinical study.
For all enrolled patients:
1) To estimate overall survival (OS) from the first dose of ipilimumab in the prior/parent study;
2) To estimate survival rate at 1 year from the first dose of ipilimumab in the prior/parent study;
3) To monitor patients who experience Immune Breakthrough Events (IBEs) after ipilimumab treatment.
For patients who receive Re-Induction in this study at the time of disease progression, following
clinical benefit (SD, PR or CR) after ipilimumab treatment:
4) Best objective response rate (BORR) following first Re-Induction in this study;
5) Disease control rate (proportion of patients with stable disease [SD], partial response [PR] or complete
response [CR]) following first Re-Induction in this study;
6) Duration of best objective response (BOR) following first Re-Induction in this study;
7) Time to BOR following first Re-Induction in this study;
8) To estimate OS following first Re-Induction in this study; |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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) | 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 | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | 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.8.5 | 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 |
|
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
| |
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 | |
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 |