E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic hormone refractory prostate cancer |
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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 |
To assess the antitumor activity of PHA-739358 administered as IV infusion according to two different dose schedules in metastatic HRPC patients progressing on standard, docetaxel-based, 1st-line chemotherapy for HRPC based on PSA response rate and to select the best dose schedule for further investigation. |
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E.2.2 | Secondary objectives of the trial |
- To further assess the antitumor activity of PHA-739358 based on objective tumor response, PSA reduction, PSA velocity, and time related end-points (duration of PSA response, progression-free survival), - To assess PHA-739358 palliative effects on tumor pain, - To assess the safety and tolerability of the two PHA-739358 schedules tested in the target population.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Adult (age >/= 18 years) male patients.
2. Histologically confirmed diagnosis of adenocarcinoma of the prostate.
3. Metastatic (stage D3 according to Jewett Staging System).
4. Hormone-refractory disease, progressing after 1st-line docetaxel-based chemotherapy. For patients with measurable disease, progression will be defined by RECIST criteria. For patients without any measurable disease, appearance of new bone lesions at bone scan and PSA progression, according to recommendations from the Prostate-Specific Antigen Working Group, will be required.
5. Patients receiving corticosteroids requested for concomitant disease other than HRPC should continue treatment at the same dose.
6. Patients receiving bisphosphonate therapy must have been on stable doses for at least 4 weeks with stable symptoms prior to enrollment.
7. Patients who have not undergone surgical castration must continue on primary androgen deprivation with LHRH analogue, if any, and testosterone must be < 50 ng/dL.
8. Prior radiotherapy is allowed provided that no more than 25% of bone marrow reserve has been irradiated and a minimum of 4 weeks have elapsed between the end of prior radiotherapy and the entry into the trial.
9. ECOG performance status 0-2.
10. Life expectancy of at least 3 months.
11. Resolution of all acute toxic effects (excluding alopecia) of any prior surgery, radiotherapy, radio-surgery or chemotherapy to NCI CTC (Version 3.0) Grade </= 1.
12. Baseline laboratory values fulfilling the following requirements: . Absolute Neutrophils Count (ANC) >/= 1,500/mm3 (>/= 1.5 x 1000000000/L); . Platelets >/= 100,000/mm3 (>/= 100 x 1000000000/L); . Hemoglobin >/= 10.0 g/dL; . Serum Creatinine </= 1.5 mg/dL (</= 133 mcmol/L); . Serum Albumin >/= 3.0 g/dL; . Total Serum Bilirubin </= 1.5 x ULN; Liver Transaminases (AST/ALT) </= 2.5 x UN; </= 5 x ULN if liver metastases are present; . Alkaline Phosphatase (ALP) </= 2.5 x ULN; </= 5 if bone metastases are present.
13. Signed and dated informed consent indicating that the patient is aware of the neoplastic nature of his disease and has been informed of the procedures to be followed, the experimental nature of the therapy, potential benefits, side effects, discomforts, risks, and alternative treatments.
14. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures.
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E.4 | Principal exclusion criteria |
1. Current enrollment in another therapeutic clinical trial.
2. Use of other investigational drugs (drugs not marketed for any indication) within 30 days prior to treatment.
3. More than one prior chemotherapy line.
4. Known brain or leptomeningeal disease (baseline computerized tomography [CT] or Magnetic Resonance Imaging [MRI] scan of the brain required only in case of clinical suspicion of central nervous system metastases.
5. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or superficial bladder cancer, or any other cancer from which the patient has been disease-free for 5 years or greater.
6. Prior treatment with radiopharmaceuticals (e.g. Strontium-89, Samarium-153) within 8 weeks prior to enrollment.
7. Major surgery, within 4 weeks or not fully recovered prior to Day 1.
8. Male patients must agree to have no intention to father a child during the study and in the following 3 months after the end of the treatment.
9. Uncontrolled hypertension with blood pressure exceeding 160/100 mmHg (Stage 2 hypertension according to the JNC 7/ NIH USA 2003 guideline).
10. Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis.
11. Cardiac dysrhythmias Grade >/= 2 according to NCI CTCAE version 3.0.
12. Known active infections, including HIV positivity.
13. History of allergic reactions to a similar structural compound, biological agent, or formulation.
14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
PSA response rate within the first three months of treatment, defined according to the recommendations from the Prostate-Specific Antigen Working Group, i.e. proportion of patient achieving at least a 50% PSA decline from baseline confirmed by a second PSA value, 4 or more weeks later. |
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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) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
Same IMP, different schedule |
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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 | 11 |
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 | 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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See protocol Section 9.2.2. |
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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 | 11 |
E.8.9.1 | In the Member State concerned days | |
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 | 11 |