E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
asymptomatic hormone-refractory prostate cancer
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MedDRA Classification |
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 single arm, prospective Phase II trial to test the safety and efficacy of intermittent chemotherapy with docetaxel (Taxotere®) and prednisone in asymptomatic, hormone-refractory prostate cance |
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E.2.2 | Secondary objectives of the trial |
- Major toxic events (percentage of patients with > G2 toxicity according to CTC AE 3.0) at treatment and re-treatment.
- Duration of each treatment holiday (days / weeks).
- Time until PSA response measured from day 1 of each treatment and re-treatment sequence respectively
- Percentage of patients with PSA and/or measurable disease-progression within or after the first, second, third or any further treatment sequence
- Time to progression (TTP) measured from day 1 of the first chemotherapy cycle until the patient goes off protocol because he is defined to be a “non responder” at defined points in the protocol, or due to any other type of progression.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Histologically proven adenocarcinoma of the prostate - Hormone refractory prostate cancer with or without metastases after definitive treatment of the primary tumor, either radical prostatectomy or definitive radiotherapy of the prostate, defined as progression under prior hormonal treatment with LH-RH analogues or orchiectomy and anti-androgens, given either together or consecutively - Irradiation of the tumor-bed allowed - Progressive disease, defined as PSA progression documented by 2 increased PSA values over a previous reference value or measurable disease progression according to the modRECIST criteria - PSA at time of study entry > 5 ng/ml (hybritech or equivalent, normal lab upper value 4 ng/ml) within 1 week prior to randomisation and < 40 ng/ml. - Age ≥18 years - WHO Performance status 0-2 - No tumor-related symptoms - Stable analgesic use is allowed - Anti-androgen treatment with Flutamide, Bicalutamide or Nilutamide should be withdrawn at least 6 weeks prior to the start of chemotherapy - Continuation of bisphosphonates allowed - Castrate level of testosterone (< 0.5 ng/ml). Patients with medical castration with LH-RH analogue must continue LH-RH analogue. - Adequate haematological functions: Hb ≥ 10 g/dl; WBC ≥ 3.500 x109/l; ANC ≥ 1,5 x109/l; platelets ≥ 100 x109/l. - Adequate liver function: Bilirubin ≤ 1,5 x UNL (upper normal level); ASAT and ALAT ≤ 1,5 x UNL. - Before patient registration / randomization, written informed consent must be given according to ICH-GCP, and national / local regulations
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E.4 | Principal exclusion criteria |
- Evidence of brain metastases. - Painful and/or destructive bone metastases for which radiation therapy, bisphosphonates or bone-seeking radionucleides are considered necessary by the treating physician. - Unequivocal tumor-related symptoms. - Increasing analgesic use, unstable pain. - Prior treatment with chemotherapy, bone-seeking radionucleides or radiotherapy involving more than 25% of bone marrow producing area. (Prior use of Estramustine phosphate and/or bisphosphonates are allowed.) - Active infection or known HIV. - History of interstitial pneumonitis or pulmonary fibrosis. - Pre-existing neuropathy (PNP ≥ G1). - Second primary cancer (except adequately treated superficial cancers e.g. superficial urothelial cancer or in situ carcinomas, skin cancer and melanoma without signs of recurrence in the past 5 years). - Concurrent treatment with other experimental drugs or anti-cancer drugs (except LH-RH agonist). - Any condition / concomitant disease not allowing chemotherapy with docetaxel and prednisone from an internal medicine point of view. (Renal insufficiency requiring dialyses; congestive heart failure or uncontrolled angina pectoris; prior myocardial infarction within 6 months of start of chemotherapy; uncontrolled hypertension or arrhythmias; dementia; instable diabetes mellitus, ulceration from diabetes mellitus or other conditions not allowing high dose corticosteroids; effusions in pericardium, pleura or abdomen symptomatic and in need of being punctured. - Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
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E.5 End points |
E.5.1 | Primary end point(s) |
PSA and/or measurable response to initial treatment and re-treatment after each treatment holiday |
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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 | 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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
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
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |