E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Hormone-Refractory Prostate Cancer (HRPC) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
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 |
The primary objective of Part 2 of the trial is to compare CNTO 328 in combination with mitoxantrone vs mitoxantrone with respect to the PFS of subjects with metastatic HRPC who have received only one prior docetaxel-based chemotherapy regimen. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of Part 2 are to evaluate and compare safety and other efficacy endpoints of CNTO 328 in combination with mitoxantrone versus mitoxantrone in subjects with metastatic HRPC who have received only one prior docetaxel-based chemotherapy regimen. In addition, pharmacodynamic biomarker and health outcomes responses will be evaluated. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible for the study, subjects must meet all of the following criteria:
1. Males aged ≥ 18 years 2. Signed informed consent obtained prior to any study-specific screening procedures 3. Histologically or cytologically confirmed adenocarcinoma of the prostate 4. Radiologically documented metastatic disease 5. At least 6 weeks of treatment with one prior docetaxel-based chemotherapy regimen for metastatic HRPC 6. Disease progression, during or within 6 months of cessation of prior docetaxel-based therapy, based on one of the following: a. Serum PSA progression, defined as a rise in at least 2 consecutive serum PSA values, each obtained at least 1 week apartor b. Radiologic disease progression: If disease progression is shown by bone scan only, then disease progression is defined by the appearance of 2 or more new bone lesions 7. Orchiectomy or testosterone < 50 ng/dL by means of pharmacological/chemical castration 8. At least 4 weeks from prior anti-cancer therapy 9. ECOG ≤ 2 10. Screening laboratory values for study entry: a. WBC count ≥ 3.0 x 109 /L and absolute neutrophil count (ANC) ≥ 1.5 x 109/L b. Hemoglobin ≥ 9.0 g/dL c. Platelet count ≥ 100 x 109/L d. AST and ALT ≤ 2.5 x ULN e. Bilirubin ≤ 1.5 x ULN f. Creatinine ≤ 1.5 x ULN 11. LVEF ≥ 50%
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria may not be enrolled in the study:
1. Prostate cancer that does not express PSA or PSA level is < 5.0 ng/mL at screening. 2. Known CNS metastases. 3. Received any investigational drug/agent within 30 days or 5 half-lives, whichever is longer. 4. Received more than one line of systemic chemotherapy for metastatic HRPC. 5. Prior mitoxantrone treatment for HRPC. 6. Prior malignancy (other than prostate cancer) except adequately treated superficial bladder cancer, basal cell or squamous cell carcinoma of the skin, or other cancer for which the subject has been disease-free for ≥ 3 years. 7. Known HIV seropositivity or known hepatitis B or C infection. 8. Planned major surgery during the study. 9. Received any mAb within 60 days of first dose of study agent. 10. Serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease, significant arrhythmias, or congestive heart failure (≥ New York Heart Association (NYHA) II; Appendix B) or myocardial infarction within the past 6 months. 11. Any uncontrolled medical condition, serious infection or the presence of clinically significant laboratory abnormalities, that places the subject at unacceptable risk by participating in the study or confounds the ability to interpret data from the study. 12. Therapy with bisphosphonates initiated < 6 weeks prior to first administration of CNTO 328. 13. Transfusion dependent anemia 14. Vaccinated with live, attenuated vaccines within 4 weeks of the first administration of CNTO 328. Inactivated injectable influenza vaccine is permitted. 15. Known allergies or clinically significant reactions to murine, chimeric, or human proteins. 16. Medical history suggesting compromised bone marrow (eg, recurrent febrile-neutropenia, neutropenic infection, multiple dose delay during prior docetaxel treatment, or required use of granulocyte colonystimulating factor [G-CSF] or granulocyte-macrophage colony-stimulating factor [GM-CSF] to meet study entry criteria). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints are safety for Part 1, and PFS (Progression Free Survival) for Part 2. |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
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) | Yes |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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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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 | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |