| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Clinically asymptomatic prostate cancer subject with a rising PSA following definitive local therapy |
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| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10060862 |
| E.1.2 | Term | Prostate cancer |
| 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 evaluate and compare the efficacy of androgen deprivation with or without Taxotere as determined by the median progression free survival (PFS) within the period of 18 months of therapy and at least 18 months follow-up. |
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| E.2.2 | Secondary objectives of the trial |
• To evaluate cancer specific survival
• To compare overall survival between the 2 treatment groups
• To evaluate patient reported outcomes as measured by 3 different assessments
In this study, molecular markers will also be evaluated (including, but not limited to, variable gene expression profiles, genetic changes and quantitative methylation of different genes, protein quantification and quantification of circulating tumor cells) for the potential to correlate with clinical and pathological risk factors and to determine if they predict the treatment outcome of high-risk prostate cancer subjects. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Diagnosis of prostate adenocarcinoma pathologically confirmed.
2. History of radical prostatectomy (pre-operative radiation therapyto the prostate or pelvis or salvage radiation after radical prostatectomy is allowed).
3. Demonstration of biochemical progression of disease based on PSA doubling time. The minimum PSA value for eligibility will be greater than or equal to 1. PSA doubling time over three values must be ≤ 9 months with a minimum of 3 weeks between assessments. PSA doubling time calculation must start at a minimum value of 0.2 (see Section 13.2). Subjects in this group may have no radiographic findings that are suspicious for metastatic disease.
4. Serum testosterone ≥ 100 ng/dl.
5. Karnofsky performance status (KPS) ≥ 70%.
6. Adequate organ function as defined by the following laboratory criteria:
WBC ≥ 3500/mm3
ANC ≥ 1500/mm3
Platelet count ≥ 100,000/mm3
Hemoglobin≥ 10.0 g/dl
Total Bilirubin ≤ ULN unless due to Gilbert’s disease
Creatinine ≤1.5 mg/dl or creatinine clearance of ≥ 60 cc/min
AST and ALT and Alkaline Phosphatase must be within the range as indicated in the protocol
7. Previous hormonal therapy is allowed provided that the total duration of therapy does not exceed 6 months.
8. Male subjects must be at least 18 years of age.
9. Subjects must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.
10. Men of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
11. Subjects must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
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| E.4 | Principal exclusion criteria |
1. Clinically significant cardiac disease (New York Heart Association Class III/IV), or severe debilitating pulmonary disease.
2. Uncontrolled serious active infection.
3. Anticipated duration of life of less than 2 years
4. Less than 5-year history of successful treatment for other cancers or concurrent active nonprostate cancer other than nonmelanoma skin tumor.
5. Peripheral neuropathy ≥Grade 2.
6. History of hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80, leuprolide, or bicalutamide.
7. Prior chemotherapy within the past 10 years (except non-taxane based chemotherapy for treatment of other cancers); concurrent treatment on another clinical trial or with any other cancer therapy including chemotherapy, immunotherapy, radiotherapy (except pre-operative radiation or salvage radiation therapy after prostatectomy), chemoembolization therapy, cryotherapy.
8. Other severe acute or chronic medical conditions including psychiatric disease(s), or significant laboratory abnormality requiring further investigation that may cause undue risk for the subject’s safety, delay or prohibit protocol participation, or interfere with the interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study.
9. Radiographic findings suspicious for metastatic disease in the treating physician’s clinical judgment. Patients who had radiographically suspicious pelvic lymph nodes prior to radical prostatectomy, but who, at the time of registration to the trial do not have suspicious adenopathy (for example, either because those nodes were resected or were irradiated post-operatively) are eligible for the protocol. Patients are eligible even if they had tumor-containing pelvic adenopathy at the time of surgery as long as at the time of registration they do not have radiographically evident nodal disease in the clinician's opinion.
10. Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol.
11. Subject unlikely to comply with protocol or research tests, eg, uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study.
12. Subject who participated in any therapeutic clinical study/ received investigational product within 30 days of screening.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Progression-Free Survival (PFS) is the primary efficacy endpoint for this study. The
PFS period will be measured as the time from randomization to the date of first
documentation of PSA progression, or radiographic progression, or death due to
prostate cancer in the absence of previous documentation of disease progression, whichever occurs first. The PSA progression is determined as follows:
a) during treatment period: PSA is checked every 12 weeks. If a measured PSA is higher than the preceding value, then the rising PSA will be confirmed in 6 weeks (+/- 1 week). If that third PSA value is higher still and the range of values is 50% above the baseline, then the patient is off study treatment. If not, the patient will remain on study treatment, and the PSA will once again be chcecked when the patient presents for a leuprolide injection
or
b) during follow-up, after completion of treatment period: progression determined as detectable PSA defined as PSA ≥0.05 ng/mL and confirmed by consecutive observation at the next scheduled visit (but no less than 2 weeks apart).
This trial will have PFS based on PSA control as primary endpoint. By consensus, post-treatment PSA changes are not described as “responses.”2 There are no clinically validated criteria for PSA “response” for subjects with noncastrate disease. Therefore, the traditional methods of efficacy reporting based on PSA percentage declines, or on the proportion of subjects showing normalization of an abnormal level do not apply to this subset of subjects. As such, we are establishing a primary endpoint of disease control for this study as time from randomization to detectable PSA, determined as PSA ≥0.05 ng/mL after prostatectomy at minimum.
A confirmatory PSA must be drawn no less than 2 weeks following the first PSA ≥0.05 ng/ml for post-prostatectomy subjects. If that confirmatory PSA also exceeds the above parameter, then the subject is taken off study and is defined as a biochemical failure. If the confirmatory PSA fails to confirm a biochemical failure, then the subject will remain on study.
Duration of Biochemical Response: Although a confirmatory PSA is required to define a biochemical failure by PSA, the time of progression will be defined as the date of the first instance in which the PSA was ≥0.05 ng/ml in post-prostatectomy.
Outcome in subjects who develop radiographically evident metastatic disease while on study will be considered treatment failures independent of their respective PSA values. These patients will be taken off study for progressive disease.
The primary analysis will be based on the intent-to-treat population.
For subjects who do not have objective disease progression and who are either still on study at the time of an analysis, are given antitumor treatment other than the study treatment, or are removed from study follow-up prior to documentation of objective disease progression, the PFS will be censored at the last date the subject was known to be progression-free. For subjects lost to follow-up without having a documented date of disease progression, the PFS will be censored on the last day the subject was known to be progression-free.
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| 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 | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | 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 | 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
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| 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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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 54 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 66 |
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