| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Castration Resistant Prostate Cancer. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060862 |
| E.1.2 | Term | Prostate cancer |
|
| 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 overall survival of subjects with castration resistant prostate cancer (CRPC), that have progressed during or following docetaxel treatment, when treated with bone-directed radiotherapy followed by ipilimumab vs bone-directed radiotherapy followed by placebo. |
|
| E.2.2 | Secondary objectives of the trial |
| Compare progression free survival (PFS) Compare PSA response rate Characterize the kinetics of tumor burden among subjects with measurable disease Characterize PSA kinetics Compare pain response Estimate changes in Quality of Life (QoL) as measured by the Medical Outcome Estimate changes in pain intensity as measured by the Brief Pain Inventory Short Form (BPI-SF) Characterize safety profile Determine presence of Human Anti-Human Antibodies (HAHA) Perform pharmacokinetic (PK) analyses. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1) Signed Written Informed Consent a) Willing and able to give informed consent. 2) Target Population a) Histologic or cytologic confirmation of adenocarcinoma of the prostate; b) At least 1 symptomatic bone metastasis which can be irradiated, or at least 1 asymptomatic bone metastasis which, in the clinical judgment of the investigator, is appropriate to be irradiated (eg, risk of fracture or cord compression); c) Have been treated by orchiectomy or are receiving a LH-RH analog, and have a testosterone level less than 50 ng/dl; d) If applicable, must have discontinued first-line anti-androgens 6 weeks prior to randomization, or other anti-androgens at least 2 weeks prior to randomization; e) Must have received at least 1 prior regimen containing docetaxel for the treatment of metastatic CRPC, consisting of at least 2 cycles of docetaxel with the first cycle administered at a dose of 75 mg/m2; f) ECOG Performance Status: i) Subjects who have received docetaxel only, must have ECOG PS 0 - 1; ii) Subjects who have received an additional anti-cancer therapy after docetaxel (including re-treatment with docetaxel), must have ECOG PS 0; g) Subjects must have progressed during docetaxel treatment or within 6 months of the last administration of docetaxel. If the subject received an additional anticancer therapy after docetaxel, they must also demonstrate signs of progression on that therapy. For eligibility purposes, progressive disease is defined as: i) Rising PSA values at a minimum of 1-week intervals and a 2.0 ng/mL minimum starting value ii) Progression per bone scan: the appearance of 2 or more new lesions iii) Progression per target lesions/measurable disease: nodal or visceral disease progression, per modified RECIST. Only lymph nodes greater than 2 cm will be considered to assess a change in size qualifying for disease progression. 3) Age and Sex a) Men ≥ 18 years of age or minimum age of consent per local regulations. |
|
| E.4 | Principal exclusion criteria |
| 1) Sex and Reproductive Status a) Sexually active fertile men not using effective birth control if their partners are women of child-bearing potential (WOCBP). 2) Target Disease Exceptions a) Subjects with radiological evidence of brain metastasis. 3) Medical History and Concurrent Diseases a) Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn’s disease are excluded from this study, as are subjects with a history of rheumatoid arthritis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis (eg, Wegener’s Granulomatosis); b) Motor neuropathy considered of autoimmune origin (eg, Guillain-Barre Syndrome); c) Patients with a prior history of pelvic (prostate) radiation associated with significant radiation proctitis within 12 months prior to the planned first infusion of blinded study drug. For the purpose of this protocol, radiation proctitis is defined as diarrhea that reached a level of Grade 2 or Grade 3, that occurred within 1 month of radiation treatment, and that was of 7 days duration or longer. d) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires; e) A serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy; f) Any other malignancy from which the subject has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, or superficial bladder cancer; g) Known HIV or Hepatitis B or Hepatitis C infection. 4) Physical and Laboratory Test Findings a) Inadequate hematologic function defined by an absolute neutrophil count (ANC) < 1,500/mm3, a platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dL; b) Inadequate hepatic function defined by a total bilirubin level &#8805; 2.5 times the upper limit of normal (ULN), AST and ALT levels &#8805; 2.5 times the ULN or &#8805; 5 times the ULN if liver metastases are present; c) Inadequate renal function defined by a serum creatinine level &#8805; 2.5 times the ULN; d) Inadequate creatinine clearance defined as less than 50 mL/min; e) Usage of greater than 120 mg of morphine (or equivalent) over a 24 hour period within 3 days of randomization, unless narcotic usage is necessitated by a symptomatic bone lesion that is likely to be palliated by protocol-specified radiotherapy. 5) Prohibited Treatments and/or Therapies a) More than 2 prior systemic anti-cancer regimens (including re-treatment with docetaxel) for metastatic CRPC; b) Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, during the course of the study, use of corticosteroids is allowed if used for treating irAEs, or adrenal insufficiencies, or if administered at doses of prednisone 5 mg BID or equivalent; c) Any non-oncology vaccine therapy used for the prevention of infectious diseases (for up to 4 weeks prior to or after any dose of blinded study drug); d) Prior treatment with any inhibitor or agonist of T cell costimulation; e) Prior strontium or samarium; f) Prior treatment on BMS study CA180227: A Randomized Double-Blind Phase 3 Trial Comparing Docetaxel Combined with Dasatinib to Docetaxel Combined with Placebo in Castration-Resistant Prostate Cancer. 6) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated; b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Efficacy: Survival will be defined as the time from date of randomization to the date of death. If the subject is lost to follow-up, survival will be censored on the last date the subject was known to be alive. Safety: Will be based on medical review of AE reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. |
|
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Immunogenecity sample testing (HAHA); QoL; ECG substudy |
|
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 48 |
| 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 | 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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