E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
patients with hormone-refractory prostate cancer (HRPC) with rising PSA |
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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 | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
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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 |
Phase I part: Determination of the recommended dose (RD) for exploration in the phase II part Phase II part: Assessment of safety of the trial regimen |
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E.2.2 | Secondary objectives of the trial |
Phase I part: Assessment of safety of the trial regimen Evaluation of induction of immune response
Phase II part: Evaluation of induction of immune response Assessment of anti-tumor activity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent in accordance with GCP and local regulatory requirements prior to trial participation 2. Male and age ≥ 18 yrs (Phase I and II) and ≤ 75 yrs (Phase II only) 3. Histologically confirmed diagnosis of adenocarcinoma of the prostate, Gleason Score available 4. Patients must have been treated with hormonal therapy and may have been treated with surgery and/ or radiation therapy 5. Progressive disease as defined by hormone-refractoriness and rise in PSA: Hormone refractoriness: Defined by a rise in PSA and/or RECIST-based progression of evaluable lesions, and/or increased number of hotspots on a bone scan, while the patient has a castrated level of testosterone. This castrated level may have been obtained by orchiectomy, or LH-RH analog ± antiandrogen. Antiandrogen must be discontinued for at least 4 weeks before study entry to exclude a withdrawal effect. Rise in PSA: Defined by a rise in PSA levels at three consecutive time points (PSA rise over nadir, separated by > 1 week, PCWG2 criteria) 6. Presence of metastatic disease is acceptable 7. ECOG performance status of 0 to 1 8. Life expectancy > 12 months as assessed by the investigator 9. Adequate organ function • Bone marrow function: Hemoglobin ≥ 10 g/ dL; Leukocytes ≥ 3000/ μL; Lymphocytes ≥ 1000/ μL; Absolute neutrophil count ≥ 1500/ μL; Platelet count ≥ 100000/ μL • Hepatic: AST and ALT ≤ 2.5 times upper limit of normal (ULN); Bilirubin ≤ 1.5 ULN • Renal: Creatinine ≤ 1.5 mg/ dL or creatinine clearance ≥ 60mL/ min 10. Concomitant LH-RH therapy continuation is acceptable11. May have had local palliative radiotherapy for bone metastasis involving less than 25% of bone marrow 12. Patients requiring bisphosphonates at the time of registration into the trial are eligible (therapy initiated at least 28 days prior to first study treatment administration) and must be continued at a constant level during the study period 13. Patients of child-producing potential must agree to use contraception while enrolled in the study and for one month after the last immunization. |
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E.4 | Principal exclusion criteria |
The following are criteria for exclusion of patients from participating in the study: 1. Other histologic type of prostate cancer (transitional cell, small cell or squamous cell cancer) 2. Symptomatic brain metastasis or leptomeningeal involvement 3. Patients having received or currently receiving chemo- or biological therapy for prostate cancer 4. Symptomatic congestive heart failure (NYHA 3 and 4); unstable angina pectoris; significant cardiac arrhythmia 5. Pulmonary disease causing dyspnea or fatigue during normal activity 6. History of seizures, encephalitis or multiple sclerosis 7. Inflammatory bowel disease e.g. Crohn’s disease or ulcerative colitis; active diverticulitis 8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy, (e.g. sarcoidosis, lupus erythematosus, rheumatoid arthritis, glomerulonephritis or systemic vasculitis), excepting autoimmune thyroiditis with only thyroid hormone replacement and stable disease > 1 year 9. Primary or secondary immune deficiency 10. History of allergy requiring medication 11. Active drug abuse or chronic alcoholism 12. Clinically significant active infections 13. Seropositive for HIV, HBV or HCV 14. History of other malignancies over the last 5 years (except basal cell carcinoma of the skin) 15. Uncontrolled medical condition considered as high risk for the treatment with an investigational drug including unstable diabetes mellitus, vena-cavasyndrome, known ascites and/or pleural effusion, symptomatic pleural effusion treated by puncture 16. Renal insufficiency requiring dialysis 17. Patients being committed to an institution by virtue of an order issued either by the judicial or the administrative authorities. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I part: Primary endpoint: occurrence of DLT before the week 5 visit in patients evaluablefor determination of RD Phase II part: Primary safety endpoints: • incidence and severity of adverse events and laboratory abnormalities, graded according to NCI-CTCAE version 3.0 criteria • occurrence of Serious Adverse Events • occurrence of treatment discontinuation due to adverse events • incidence of treatment emergent autoimmune disease or development of autoimmune antibodies |
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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 | 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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |