E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
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 |
|
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 estimate the rate of grade 2/3/4 diarrhea in patients treated with intravenous MDX-010 BMS-734016 at 10 mg/kg when given with either prophylactic oral budesonide Entocort EC or placebo. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the following in this patient population i Safety; ii Best objective response rate best response of CR or PR ; iii Progression Free Survival PFS Rate at Week 12; iv Disease control rate best response of CR PR SD ; v Progression free survival PFS ; vi Overall survival OS ; vii Duration of best objective response; and viii Time to best objective response. 2 To estimate the rates of other drug-related adverse events when MDX-010 BMS-734016 is given with prophylactic oral budesonide Entocort 63195; EC or placebo. 3 To identify potential predictors of response by analyzing messenger RNA mRNA expression, protein profiling and immunologic profiling in pre-treatment optional tumor biopsies. 4 To compare pre- and post-treatment mRNA expression, protein profiling and immunologic profiling in tumor specimens optional and peripheral blood mononuclear cells PBMCs . |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Signed written informed consent a Voluntary signed and dated institutional review board IRB /independent ethics committee IEC approved informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performing protocol-related procedures that are not part of standard patient care. 2 Target population a Able to comply with visits/procedures required by the protocol. b Life expectancy of at least 4 months. c ECOG performance status score 0-1 Appendix 1 . d Histologic or cytologic diagnosis of unresectable Stage III or IV malignant melanoma excluding ocular melanoma . e Measurable disease as defined in Section 3.3.3.2. f At least 4 Weeks must have elapsed since the last chemotherapy, immunotherapy, hormonal therapy, radiotherapy or major surgery and the beginning of protocol therapy. At least 6 Weeks for nitrosoureas, mitomycin C and liposomal doxorubicin. g Toxicity related to prior therapy must either have returned to 8804; grade 1, baseline, or been deemed irreversible. Men and women, ages 18 and above. |
|
E.4 | Principal exclusion criteria |
Sex and Reproductive Status a WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the study. b WOCBP using a prohibited contraceptive method. c Women who are pregnant or breastfeeding. d Women with a positive pregnancy test on enrollment or prior to study drug administration. e Sexually active fertile men who are unwilling or unable to use a barrier contraceptive eg, condom or whose partners are WOCBP not using a method of birth control from the time of enrollment and for 12 Weeks after participation in the study. 2 Target Disease Exclusion a 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, carcinoma in situ of the cervix. b Ocular melanoma. 3 Medical History and Concurrent Diseases a Active, untreated central nervous system CNS metastasis including metastasis identified during screening MRI or contrast CT . b Autoimmune disease Patients with a history of Inflammatory Bowel Disease are excluded from this study as are patients with a history of autoimmune disease e.g. Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease whose possible progression during treatment would be considered by the Investigator to be unacceptable. Patients with a history of well-controlled and/or clinically manageable autoimmune disease e.g. vitiligo, well-controlled thyroid disease, mild psoriasis may be considered for inclusion in consultation with the BMS Medical Monitor. c 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; d Positive screening tests for HIV, HepB, and HepC. If positive results are not indicative of true active or chronic infection, the patient can be admitted after discussion with and agreement by the BMS Medical Monitor. Prohibited Therapies and/or Medications a Exposure to any investigational products within 4 Weeks prior to Day 1 of treatment. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
To estimate the rate of grade 2/3/4 diarrhea in patients treated with intravenous MDX-010 BMS-734016 at 10 mg/kg when given with either prophylactic oral budesonide Entocort EC or placebo. To evaluate the following in this patient population i Safety; ii Best objective response rate best response of CR or PR ; iii Progression Free Survival PFS Rate at Week 12; iv Disease control rate best response of CR PR SD ; v Progression free survival PFS ; vi Overall survival OS ; vii Duration of best objective response; and viii Time to best objective response. 2 To estimate the rates of other drug-related adverse events when MDX-010 BMS-734016 is given with prophylactic oral budesonide Entocort 63195; EC or placebo. 3 To identify potential predictors of response by analyzing messenger RNA mRNA expression, protein profiling and immunologic profiling in pre-treatment optional tumor biopsies. 4 To compare pre- and post-treatment mRNA expression, protein profiling and immunologic profiling in tumor specimens optional and peripheral blood mononuclear cells PBMCs . |
|
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) | 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 | 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 |
|
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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |