| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | | Hormone Refractory Metastatic Prostate Cancer | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10062904 | | E.1.2 | Term | Hormone-refractory prostate cancer | |
| 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 determine whether XRP6258 in combination with prednisone improves overall survival (OS) when compared to mitoxantrone in combination with prednisone | |
| E.2.2 | Secondary objectives of the trial | ·To compare efficacy between the two treatment arms:
-PSA Response
-PSA Progression
-Progression Free Survival (PFS) defined as the first occurrence of any of the following events: tumor progression (RECIST), PSA progression, Pain progression or death due to any cause.
-Overall Response Rate (ORR)
-Pain Response
-Pain Progression
·To assess the overall safety of XRP6258 in combination with prednisone
·To assess the pharmacokinetics of XRP6258 and its metabolite, PR123142, in this patient population and effect of prednisone on the pharmacokinetics of XRP6258 | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | The Patient must have:
1.Diagnosis of histologically or cytologically proven prostate adenocarcinoma, that is refractory to hormone therapy and previously treated with a Taxotere®-containing regimen. Patient must have documented progression of disease during or within 6 months after prior hormone therapy and disease progression during or after Taxotere®-containing therapy.
2. Patient must have either measurable or non-measurable disease.
·Patient with measurable disease must have documented progression of disease by RECIST criteria demonstrating at least one visceral or soft tissue metastatic lesion (including new lesion). This lesion must measure at least 10 mm in the longest diameter (or two times the slice thickness) on spiral CT scan or MRI (chest, abdomen, pelvis) or 20 mm on conventional CT or Chest X-ray for biopsy proven, clearly defined lung lesion surrounded by aerated lung. (Previously irradiated lesions, primary prostate lesion, and bone lesions will be considered non-measurable disease)
. Patient with non-measurable disease must have documented rising PSA levels or appearance of new lesion. [Rising PSA is defined as at least two consecutive rises in PSA to be documented over a reference value (measure 1) taken at least one week apart. The first rising PSA (measure 2) should be taken at least 7 days after the reference value. A third confirmatory PSA measure is required (2nd beyond the reference level) to be greater than the second measure and it must be obtained at least 7 days after the 2nd measure. If this is not the case, a fourth PSA measure is required to be taken and be greater than the 2nd measure. The third (or the fourth) confirmatory PSA should be taken within 4 weeks prior to randomization]
3.Received prior castration by orchiectomy and/or Luteinizing Hormone-Releasing Hormone (LH-RH) agonist with or without antiandrogen, antiandrogen withdrawal, monotherapy with estramustine, or other hormonal agents. (A prior treatment by antiandrogen is not mandatory. However, if the patient has been treated with antiandrogens, and PSA is above 5 ng/mL at the last administration of antiandrogens, presence or absence of antiandrogen withdrawal syndrome* should be confirmed prior to the study entry). (LH-RH agonist treatment should continue during the study treatment period. Chlormadinone acetate or flutamide must have been stopped at least 4 weeks prior to, while bicalutamide must have been stopped at least 6 weeks prior to, the last PSA evaluation). (* The antiandrogen withdrawal syndrome is a decrease in PSA seen upon stopping an antiandrogen such as chlormadinone acetate, flutamide, or bicalutamide; this occurs because the antiandrogen has induced a mutation in the androgen receptor which is allowing the antiandrogen to stimulate prostate cancer growth rather than inhibit it)
4.Life expectancy > 2 months
5.Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 – 2 (i.e., patient must be ambulatory, capable of all self-care, and up and about more than 50% waking hour).
| |
| E.4 | Principal exclusion criteria | 1.Previous treatment with mitoxantrone
2. Previous treatment with less than 3 cycles or<225 mg/m² cumulative dose of Taxotere (or docetaxel)
3. Radiotherapy to > 40% of bone marrow. Prior treatment with one dose of a bone-seeking isotope is allowed, but 8 weeks must have elapsed after samarium-153 and P-32 and 12 weeks after strontium-89 prior to frist study drug administration.
4. Active grade ≥2 peripheral neuropathy
5. Active grade ≥2 stomatitis
6.Active secondary cancer including prior malignancy from which the patient has been disease-free for ≤ 5 years (However, adequately treated superficial basal cell skin cancer before 4 weeks prior to entry can be eligible to the study)
7.History of severe hypersensitivity reaction (≥ grade 3) or intolerance to prednisone
8.Inadequate organ function as evidenced by the following peripheral blood counts, and serum chemistries at enrollment:
·Neutrophils ≤ 1.5 x 109/L
·Hemoglobin ≤ 10 g/dL
·Platelets ≤ 100 x 109/L
·Total bilirubin ≥ Upper limit of normal (ULN)
·AST (SGOT) ≥ 1.5 x ULN
·ALT (SGPT) ≥ 1.5 x ULN
·Creatinine ≥ 1.5 x ULN
9.Left ventricular ejection fraction ≤ 50% by multi-gated radionuclide angiography (MUGA) scan or echocardiogram
10.Concurrent or planned treatment with strong inhibitors of cytochrome P450 3A4/5. (A one week washout period is necessary for patients who are already on these treatments) | |
| E.5 End points |
| E.5.1 | Primary end point(s) | | ·OS will be assessed from the date of randomization to the date of death (whatever the cause). | |
| 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 | Information not present in EudraCT |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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 | |
| 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 | | Duration of the study includes 24 months of recruitment plus a maximum of 2 years of long-term follow-up in order to assess the OS for the overall population. The study-cut off will be achieved 6 months after the last enrolled patient. | |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
