E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
metastatic castrate-resistant prostate cancer |
metastazující kastračně rezistentní karcinom prostaty |
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E.1.1.1 | Medical condition in easily understood language |
metastatic castrate-resistant prostate cancer |
metastazující kastračně rezistentní karcinom prostaty |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
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 |
The clinical trial’s objective is to estimate the survival rate of patients 34 months after randomization, estimate the proportion of patients without progression 34 months after randomization, evaluate quality of life and the influence on the pain scale scoring using the standardized EORTC QLQ-C30 (version 3.0) questionnaire and the incidence of adverse events.
An exploratory objective is to search for potential biomarkers that could play a role as prognostic factors, indicate the biological effect of ACI on the immune-reponse or identify a subgroup of patients profiting from cancer immunotherapy based on gene expression profiling.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
I-1) Men aged ≥ 18 years
I-2) Histologically confirmed prostate cancer
I-3) Presence of metastatic bone disease according to at least one of the following modalities: bone scan (scintigraphy, PET-CT), confirmed pathological fracture, evidence of bone metastases confirmed by MRI or CT
I-4) Presence of progression defined as at least one of the following:
I-4a) PSA level increasing by at least 2 ng/mL at an interval of at least 14 days with an absolute value ≥ 5 ng/mL and ≥ 50% above the PSA minimum reached during the ADT (androgen deprivation therapy) or above the level prior to treatment, if there was no response.
I-4b) Two or more new lesions discovered on the bone scan or CT or MRI as compared with the preceding scan
I-5) Continuing castrate condition: Patients who did not undergo surgical orchiectomy have to continue hormone drug therapy (GnRH/LHRH analogs) to maintain the castrate level of serum testosterone ≤ 1.7 nmol/l (50 ng/dl). The castrate condition has to be at least 3 months before enrolment to the study and continue for the study duration.
I-6) The following laboratory values: WBC > 4 x 10(9)/L, ANC ≥ 1.5x 10(9)/L, platelet count > 100 x 10(9)/L, Hb ≥ 90 g/L, Hct > 30%, Creatinine under 1.5 times the upper limit of normal, bilirubin, AST and ALT under 1.5 times the upper limit of normal.
I-7) ECOG 0-2 Performance Status
I-8) Signed informed consent to participate in the study
I-9) Recovery from primary local surgery, radiotherapy or orchiectomy.
I-10) At least 8 weeks from radioisotope therapy (Samarium-153, Strontium -89 or similar) |
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E.4 | Principal exclusion criteria |
E-1) Sexually active fertile men not using effective birth control, if their partners are of fertile age and of child-bearing potential
E-2) Comorbidities of the patient
E-2a) HIV-positive
E-2b) Active hepatitis B or C
E-2c) Active bacterial, viral or mycotic infection requiring systemic treatment
E-2d) Clinically significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia in previous 6 months, percutaneous coronary intervention or surgical revascularization in the past 6 months, heart failure NYHA II-IV, known left ventricular dysfunction with ejection fraction < 40% or haemodynamically significant arrhythmias or conduction problems, unless treated with permanent cardiac pacing.
E-2e) Pleural or pericardial effusion of any CTC grade
E-2f) Peripheral neuropathy CTC Grade ≥ 2.
E-2g) Other uncontrolled coexisting condition, uncompensated psychiatric illness or social situation that would limit patient’s compliance.
E-2h) Patients with a history of malignancy other than non-melanoma skin cancer.
E-2i) Unresolved ongoing urinary tract obstruction
E-2j) Active autoimmune disease requiring therapy
E-2k) History of primary immunodeficiency
E-3) Allergy and adverse drug reactions
E-3a) History of allergic reaction to a compound of the same or similar structure as medication used in this study.
E-3b) History of anaphylaxis or other severe reaction following vaccination
E-4) Any other serious reason the Investigator considers the patient should not participate in the study
E-5) Patients already treated with chemotherapy for prostate cancer (except estramustine)
E-6) Patients with brain and leptomeningeal metastases
E-7) Participation in another clinical trial or administration of another investigational medicinal product within 30 days preceding the screening
E-8) Treatment with antiandrogens, inhibitors of adrenal androgen production, or any other anti-tumor hormone therapy ongoing on the day of screening or in preceding 4 weeks except GnRH/LHRH analogs
E-9) Immunotherapy other than specified in this protocol
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E.5 End points |
E.5.1 | Primary end point(s) |
• The survival rate of patients 34 months after randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•The survival rate of patients without disease progression and without PSA progression 34 months after randomization
•The survival rate of patients without disease progression 34 months after randomization
•Incidence of adverse events
•Quality of life as per standardized EORTC QLQ-C30 questionnaire, version 3, European Organization for Research and Treatment of Cancer
•Pain scale influence scoring as per standardized EORTC QLQ-C30 questionnaire version 3, European Organization for Research and Treatment of Cancer
Exploratory endpoints
•Immune response
•Gene expression profiling, and/or expression levels of a defined set of immune or cancer-related genes, respectively |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patient group receiving only standard of care chemotherapy |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The study will be terminated by the Sponsor as soon as the last surviving study patient undergoes the follow-up visit 24 months after the end of treatment. |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |