E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Hormone- Refractory Prostate Cancer |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10001186 |
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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 |
This is a randomized phase II trial to evaluate the toxicity and activity (in terms of PSA response) of the combination of docetaxel and oblimersen in hormone refractory prostate cancer. The trial is randomized against docetaxel alone which will serve as a reference group to further validate the sample used in the trial. |
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E.2.2 | Secondary objectives of the trial |
time to progression, toxicity, survival |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
♦ Histologically proven prostate adenocarcinoma ♦ Hormone refractory prostate cancer defined as progression under prior hormonal treatment with LH-RH analogues or orchiectomy and anti-androgens, given either together or consecutively. ♦ Progressive disease is defined as PSA progression documented by 2 increased PSA values over a previous reference value. PSA fluctuations should be handled as defined in chapter 7.1. ♦ Patients must have a demonstrated continued elevation of PSA for at least 6 weeks after discontinuation of antiandrogens prior to registration on study ♦ PSA greater or equal to 5 ng/ml (hybritech or equivalent) within 1 week prior to randomisation ♦ No clinical evidence of brain metastases ♦ No evidence of painful and/or destructive bone metastases for which radiation therapy, bisphosphonates or bone-seeking radionucleides are considered necessary by the treating physician. Other bone metastases are allowed. ♦ Age ≥18 years ♦ WHO Performance status 0-2 ♦ No regular (daily) intake of opioid analgesics ♦ No prior treatment with chemotherapy, bone-seeking radionucleides or radiotherapy involving more than 25% of marrow producing area. (Prior use of Estramustine phosphate and/or bisphosponates are allowed). ♦ No prior hormonal manipulation with PC-SPES within the last 6 weeks prior to entry on study ♦ Anti-androgen treatment with Flutamide, Bicalutamide or Nilutamide should be withdrawn at least 6 weeks prior to randomization. ♦ No concurrent treatment with other experimental drugs or anti-cancer drugs (except LH-RH agonist) nor bisphosphonates. ♦ Castrate level of testosterone (<= 50 ng/mL). Patients with medical castration with LHRH analogue must continue LHRH analogue ♦ Adequate venous access ♦ Adequate hematological functions as assessed by Hb ≥ 10 g/dl WBC ≥ 3.500 109/l, ANC ≥ 1.5 109/l , and platelets ≥ 100 109/l. ♦ Adequate liver function as assessed by bilirubin ≤ upper limit of the normal range (UNL) and ASAT ≤ 1.5 x UNL and ALAT ≤ 1.5 x UNL ♦ Adequate renal function as assessed by serum creatinine ≤ 1.5 xULN or calculated creatinine clearance ≥ 50 ml/min according to Cockcroft formula. (see Appendix C for the formula) ♦ Partial thromboplastin time (PTT) <= 1.5xUNL and Prothrombin time (PT) <=1.5xUNL (or INR<=1.3) ♦ No known hypersensitivity to oligonucleotides or any component of the oblimersen formulation or to drugs formulated with polysorbate. No hypersensitivity to phosphorothioates. ♦ No CVA or transient ischemic attack or myocardial infarction attacks within the past 6 months ♦ No active infection, no known HIV ♦ No history of interstitial pneumonitis or pulmonary fibrosis ♦ No unstable angina or pulmonary embolism, no uncontrolled hypertension ♦ No history of deep venous thrombosis within 6 months prior to entry on study ♦ No pre-existing neuropathy ♦ No second primary cancer (except adequately treated superficial urothelial or skin cancer without signs of recurrence in the past 5 years) ♦ Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial ♦ Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
Patients can only be randomized in this trial once |
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E.4 | Principal exclusion criteria |
Please refer to Inclusion Criteria above. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints
1. PSA response defined as a 50% decline from baseline value confirmed by a second value
obtained at least 4 weeks apart according to Bubley criteria
2. Occurrence of Major toxic events
Any grade 4 haematological and non hematological toxicity except asymptomatic grade 4 neutropenia (ANC<500/mm3) lasting less than 7 days
Febrile neutropenia grade 3 for > 5 days or any Grade 4 febrile neutropenia sepsis (=grade 3 or 4) Severe (grade 3 or 4) hemorrhage-bleeding associated with grade>2 thrombocytopenia (<50.000/mm3)
· Renal toxicity grade 3 or 4 (serum creatinine > 3xULN or need of dialysis)
· Stop of treatment due to unacceptable toxicity
· Death at least possibly due to toxicity
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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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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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End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis
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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 | 4 |
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 | 4 |