Hormone Refractory Metastatic Prostate Cancer MedDRA version: 8.1 Level: LLT Classification code 10062904 Term: Hormone-refractory prostate cancer
Conditions
Interventions
Product Code: XRP6258
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 1831133-96-2
Current Sponsor code: RPR116258
Concentration unit: mg/ml milligram(s)/millilitre
Concentratio
Sponsors
sanofi aventis recherche et developpement
Eligibility
Sex/Gender
Male
Inclusion criteria
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% of waking hour). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous treatment with mitoxantrone 2. Previous treatment with less than 3 cycles or 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 first 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether XRP6258 in combination with prednisone improves overall survival (OS) when compared to mitoxantrone in combination with prednisone ;Secondary Objective: ·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;Primary end point(s): ·OS will be assessed from the date of randomization to the date of death (whatever the cause). | — |
Countries
Czech Republic, Denmark, Finland, Germany, Hungary, Italy, Netherlands, Sweden, United Kingdom
Outcome results
None listed