E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone refractory prostate cancer (HRPC) |
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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 |
The primary objectives of this study are to evaluate the efficacy and safety of treatment with CNTO 95 in combination with docetaxel and prednisone compared with docetaxel and prednisone without CNTO 95 in subjects with metastatic HRPC. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of this study are to evaluate the effect of docetaxel and prednisone with or without CNTO 95 on αv integrin-signaling pharmacodynamic biomarkers in blood, pain intensity and response/progression, overall prostate cancer symptom benefit, and the population PK of CNTO 95 in subjects with metastatic HRPC. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The substudy will take place in the US only. |
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E.3 | Principal inclusion criteria |
1. Are male ≥ 18 years of age.
2. Have histologically or cytologically confirmed adenocarcinoma of the prostate.
3. Have radiologic or clinical evidence of metastatic disease.
4. Have progressive hormone-refractory disease after orchiectomy or gonadotropin-releasing hormone analog and/or antiandrogen treatment within 6 months prior to the first study agent administration, documented by at least 1 of the following: a. Transaxial imaging (CT or MRI) tumor progression b. Rise in 2 consecutive PSA values obtained 14 days apart c. Radionucleotide bone scan with at least 2 new lesions
5. Have an ECOG score ≤ 2.
6. Have adequate bone marrow, liver, and renal function, defined as follows: a. Absolute neutrophil count (ANC) ≥ 1.5 x 10(9)/L b. Hemoglobin ≥10 g/dL (without transfusion) c. Platelets ≥ 100 x 10(9)/L d. AST and ALT < 2.5 x ULN e. Alkaline phosphatase < 5 x ULN f. Total bilirubin within normal limits g. Creatinine ≤ 1.5 mg/dL h. Activated partial thromboplastin time (aPTT) and prothrombin time (PT) ≤ 1.5 x ULN
7. Have testosterone < 50 ng/mL for subjects without surgical castration. Testosterone level will not be documented for subjects who have been surgically castrated.
8. Have serum PSA ≥5.0 ng/mL.
9. Have a life expectancy > 12 weeks.
10. Have at least 4 weeks from previous major surgery to date of first study agent administration. Subjects must have recovered or stabilized from previous surgery.
11. Have discontinued flutamide > 4 weeks prior to the first study agent administration, or have discontinued nilutamide or biclutamide > 6 weeks prior to the first study agent administration. If the subject experiences a hormonal treatment withdrawal response (including a lowering of PSA that was previously rising and/or symptomatic improvement), he will not be eligible for this study. If at a future time the subject has a new rise in PSA, he may be rescreened to determine eligibility for study participation.
12. Use appropriate contraception (eg, condom) for the duration of the study and for 3 months after the last study treatment.
13. Provide signed and dated informed consent(s) prior to any study-specific procedures and agree to comply with all protocol-specified procedures. |
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E.4 | Principal exclusion criteria |
1. Have known CNS metastases.
2. Had prior systemic nonhormonal therapy for HRPC. For the purpose of this study, Estramustine is considered a hormonal treatment; thus, it will be allowed as a prior treatment for subjects in this study.
3. Received any investigational drug/agent within 30 days or 5 half-lives, whichever is longer.
4. Had a prior malignancy (other than prostate cancer) except for 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 ≥ 5 years.
5. Have known HIV seropositivity or known hepatitis B or C infection.
6. Have planned major surgery during the study.
7. Had prior radiotherapy to > 25% of the marrow-containing skeleton. Palliative radiotherapy (eg, for pain, fracture prevention) to control a small area of metastatic bone disease may be permitted if the subject has recovered from the effects of radiotherapy or if the radiotherapy was 6 weeks prior to administration of the first study agent infusion (whichever is longer).
8. Have peripheral neuropathy > Grade 1.
9. Have a history of uveitis.
10. Have taken any over-the-counter or herbal treatment for prostate cancer within 4 weeks prior to the first study agent administration.
11. Have a serious concurrent illness or significant cardiac disease characterized by significant ischemic coronary disease, significant arrhythmias (requiring active treatment), or congestive heart failure (≥ NYHA II) or myocardial infarction within the previous 6 months.
12. Have 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.
13. Requires hematopoietic growth factors or transfusion of blood products to meet eligibility criteria.
14. Had prior use of radionucleotide therapy (eg, Strontium(89), Samarium).
15. Undergoing concurrent immunotherapy, biotherapy, radiotherapy, investigational therapy, or steroid therapy other than that included in this protocol (except for topical or inhaled steroids, or unless clinically indicated [eg, for reactions to IV contrast, allergic reactions that develop during the study, severe nausea, vomiting]). Subjects on stable doses of steroids for treatment of noncancerous conditions will be allowed to continue on these during the study only if maintained at the same dose (ie, the dose may not be increased during this study), at the discretion of the investigator.
Furthermore, subjects undergoing concurrent cancer treatment are not to be enrolled, with the exception of those receiving bisphosphonates or luteinizing hormone-releasing hormone (LHRH) agonists, as described in Section 7.2 of this protocol.
16. Requires concurrent anticoagulation therapy (except for low-dose prophylaxis).
17. Have known hypersensitivity to docetaxel or its components.
18. Have a history of anaphylaxis or severe allergic reaction(s) to human Ig therapy or polysorbate 80 (formulation components of CNTO 95).
19. Has history of bleeding diathesis.
20. Had recurrent arterial or venous thromboembolism within 6 months preceding enrollment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is progression-free survival (PFS), defined as the time from the date of randomization until the first documented sign of disease progression (radiographic, clinical, or both) or death due to any cause, whichever occurs sooner. |
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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 | Yes |
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 | Yes |
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 | 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 | 20 |
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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The last follow-up visit among all treated subjects. |
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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 | 5 |
E.8.9.1 | In the Member State concerned days | 17 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 17 |