E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Castration Resistant Prostate Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10036909 |
E.1.2 | Term | Prostate cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 chemotherapy-naïve Castration Resistant Prostate Cancer (CRPC) who have been randomized to ipilimumab vs placebo. |
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E.2.2 | Secondary objectives of the trial |
• Compare Progression Free Survival (PFS) • Compare time to pain progression • Compare time to subsequent non-hormonal systemic therapy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Signed Written Informed Consent
2) Target Population a) Histologic or cytologic confirmation of adenocarcinoma of the prostate; b) Have been treated by orchiectomy or are receiving a LH-RH analog, and have a testosterone level ≤ 50 ng/dL; c) Metastatic disease by any 1 of the following modalities: CT, MRI, bone scan; d) Progression during hormonal treatment. 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 (as defined by the Prostate Cancer Working Group 2 [PCWG2])27 OR; ii) Progression per bone scan: the appearance of 2 or more new lesions, OR; iii) Progression per target lesions/measurable disease: nodal progression, per modified RECIST 1.0. Only lymph nodes greater than 2 cm will be considered to assess a change in size qualifying for disease progression. e) Anti-androgens (bicalutamide, flutamide, nilutamide) or adrenal androgen production inhibitors (aminoglutethamide or ketoconazole) should be discontinued prior to starting study therapy: i) For subjects with a history of response to an anti-androgen or adrenal androgen production inhibitor and subsequent progression while on that anti-androgen should be assessed for anti-androgen withdrawal response for 4 weeks, and must demonstrate progression off anti-androgen prior to enrollment; ii) For subjects that have never responded to anti-androgens, observation for anti-androgen withdrawal response is not necessary; however, a 2 week washout period is required prior to start of study therapy f) ECOG Performance Status 0-1; g) Asymptomatic or minimally symptomatic. i) Minimally symptomatic disease will be defined as the following: (1) If cancer related pain is present, the pain must be rated by the patient as ≤ 4 according to item #3 of the BPI-SF for all days during the 5 day assessment period prior to randomization; (2) Any cancer related pain must not require any opiate analgesics (including codeine and dextropropoxyphene) over the 5 day assessment period prior to randomization.
3) Age and Sex a) Men ≥ 18 years of age or minimum age of consent per local regulations. |
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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 childbearing potential (WOCBP).
2) Target Disease a) Visceral (liver, lung or brain) metastases are not permitted;
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. Subjects with a history of symptomatic disease (eg, rheumatoid arthritis, autoimmune thyroiditis (eg, Hashimoto’s disease), autoimmune hepatitis, systemic progressive sclerosis (scleroderma), Systemic Lupus Erythematosus, autoimmune vasculitis (eg, Wegener’s Granulomatosis); Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barré Syndrome) are excluded from this study. Patients with vitiligo are eligible to enter the study. b) Less than 1 year since resolution of ≥ Grade 2 toxicity related to pelvic-targeted therapy (e.g radiation enteritis); c) Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent or completing questionnaires; d) A serious uncontrolled medical disorder that, in the opinion of the investigator, would impair the ability of the subject to receive protocol therapy; e) Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured and needing no subsequent therapy, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the breast; f) 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 ≥ 2.5 times the upper limit of normal (ULN), AST and ALT levels ≥ 2.5 times the ULN or ≥ 5 times the ULN if liver metastases are present; c) Inadequate renal function defined by a serum creatinine level ≥ 2.5 times the ULN; d) Inadequate creatinine clearance defined as less than 50 mL/min;
5) Prohibited Treatments and/or Therapies a) Prior treatment with any immunotherapy for prostate cancer, including autologous prostate cancer vaccine sipuleucel-T (Provenge®); b) Prior or ongoing cytotoxic therapy for metastatic prostate cancer (eg, docetaxel, mitoxantrone, estramustine); c) Pelvic-targeted radiotherapy within 3 months prior to the start of study therapy; d) 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; e) 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); f) Prior treatment with any inhibitor or agonist of T-cell costimulation; g) Prior radioisotope therapy (eg, Strontium-89, Samarium-153 or similar agents);
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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of overall survival (OS) will be defined as the time from the date of randomization until the date of death. For those subjects who have not died, OS will be censored at the last date the subject was known to be alive. |
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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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity (HAHA); Outcomes Research Assessments |
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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) | 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
| 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 | 42 |
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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For all subjects, contact will be made every 12 weeks to evaluate Overall Survival (OS) and collect data on the initiation of subsequent therapy for prostate cancer.
The final analysis of OS will be performed when 379 events (deaths) have been observed. This is expected to occur ~52 months after the first subject has been randomized. Additional survival follow-up may occur after the final OS analysis to further characterize long-term survival for subjects randomized in this study.
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |