E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prostatic carcinoma with pathological stage pT3a-b R0-1 N0M0 / pT2R1 N0M0, Gleason score 5-10 |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036955 |
E.1.2 | Term | Prostatic carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 investigate the potential benefit of a combined adjuvant treatment consisting of short term androgen suppression in addition to immediate or early salvage post-operative RT in comparison to immediate or early salvage post-operative RT alone, for improving the biochemical progression free survival of patients who have undergone radical prostatectomy for cT1-2-3a cN0M0 prostate cancer with baseline PSA ≤ 30 ng/ml and who present post-operatively with pathologic stage pT2 R1 / pT3a-b R0-1 cN0M0, Gleason score 5-10 and an undetectable or very low < 0.2 ng/ml) post-operative PSA. |
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E.2.2 | Secondary objectives of the trial |
A translational research study involving proteomics and collection of tissue micro-arrays for future research will be carried out in selected centers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with clinical stage cT1-2-3aN0M0 prostate cancer clinically assessed after a preoperative work-up including physical examination, chest X-ray, bone scan, CT scan or MRI of the entire pelvis and abdomen.
- Pre-operative PSA ≤ 30ng/ml
- Presenting after radical prostatectomy (all techniques
allowed:retropubic, laparoscopic or perineal) with:
*Gleason sum 5-10
*Pathologic stage pT2R1 (positive surgical margins with at least a tumor trans-section higher than 2 mm) or pT3a-b (irrespective of margin status)
*Negative lymph node (LN) status (pN0) by LN sampling or LN XML File Identifier: PCovc+DvFWSFlF2RzJBwTuErsfw=
Page 11/25 dissection or cN0 (by MRI) pNx. *Post-operative PSA undetectable (PSA is below the detection level of the laboratory) within 3 months of surgery
- Age ≤ 80 years.
- WHO performance status 0-1.
- Normal organ functions as shown by all of the following (measured within 2 weeks prior to randomization):
*hemoglobin ≥ 110 g/l
*WBC ≥3 x 109/l
*platelet count ≥ 100 x 109/l
- Medically fit to receive radiation therapy. Preferably the patient should be fully continent at randomization.
- Before patient randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. Patients can be randomized in this trial only once.
- To enter the trial in the "immediate post-operative" setting
* External irradiation must be planned to start within 26 weeks after surgery. Randomization should ideally take place within 22 to maximum 25 weeks after surgery and minimum 1 week before the start of the post-operative treatment and the PSA should be undetectable or very low (< 0.2 ng/ml) within 2 weeks before randomization.
- To enter the trial in the "early salvage" setting
* biochemical failure defined by rising PSA documented
* Either by 3 PSA measurements (nadir and 2 consecutive increases measured at least 2 weeks apart) with final PSA value > 0.1 ng/ml and ≤ 0.5 ng/ml;
* Or, in the case where the 3rd value is not > 0.1 ng/ml, by 4 PSA measurements (nadir and 3 consecutive increases measured at least 2 weeks apart).
* Final measurement should be within 2 weeks before randomization and ≤ 0.5 ng/ml. Salvage treatment must be planned to start within 2 months after biochemical
failure. Randomization should take place minimum 1 week before starting the salvage treatment. |
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E.4 | Principal exclusion criteria |
- prior pelvic irradiation.
- prior bilateral orchiectomy.
- prior chemotherapy within the 5 years prior to randomization.
- prior hormonal treatment except neo-adjuvant treatment lasting ≤ 3 months.
- other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has been disease free for at least 5 years.
- 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 randomization in the trial.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary trial endpoint is biochemical progression-free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The distant-metastases free survival is counted from the day of randomization to the day of the first record of appearance of distant metastases or of death of any cause. Second cancers, biochemical progression, clinical evidence of loco-regional only progression are not
considered events in terms of this endpoint.
Patients without any of the events of interest are censored at the date of the last follow-up. |
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E.5.2 | Secondary end point(s) |
The secondary endpoints considered in this study are the acute and late treatment toxicity, clinical progression-free survival, overall survival, distant-metastatis free survival and quality of life. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Side effects of the treatment will be assessed using the International Common Terminology Criteria
for Adverse Events (CTCAE), version 3.0 scoring system. |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life assessment; Translational Research on Biological material |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 | No |
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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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 locked 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 | 7 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |