E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
(mHRPC) after failure of a docetaxel-based chemotherapy regimen |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062904 |
E.1.2 | Term | Hormone-refractory prostate cancer |
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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 demonstrate superiority in the overall survival (OS) of patients with progressive mCRPC treated with sunitinib plus prednisone (SP) versus placebo plus prednisone (PP) after failure of a docetaxel-based chemotherapy regimen. |
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E.2.2 | Secondary objectives of the trial |
•To demonstrate superiority in the progression-free survival (PFS) of patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen. • To compare the objective response rate (ORR) and duration of response (DR) in patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen. • To compare patient reported outcomes (PROs) of pain severity, health-related quality of life, prostate cancer-specific symptoms, and general health status in patients with progressive mCRPC treated with SP versus PP after failure of a docetaxel-based chemotherapy regimen. • To evaluate the safety and tolerability of sunitinib in combination with prednisone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Histologically- or cytologically-confirmed adenocarcinoma of the prostate. 2. Metastatic castration-resistant prostate cancer (refractory to androgen ablation). Patients must have surgical or ongoing chemical castration, with baseline testosterone level ≤50 ng/dL. 3. Patients must have disease that has failed one prior docetaxel-based chemotherapy regimen for the treatment of metastatic disease, defined as progression of disease on or after treatment (docetaxel-resistant), or be considered docetaxel-intolerant (discontinued treatment due to unacceptable toxicity, as judged by the treating physician or by the patient). In the event both disease progression and drug intolerance are observed during prior docetaxel-based treatment, disease progression will be considered the dominant entry criterion. 4. Patients must have documented evidence of progressive disease defined by either: • PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of one week apart with the last result being at least 2.0 ng/mL, • New or increasing non-bone disease (RECIST), or • Positive bone scan with 2 or more new lesions (PCWG2). 5. ECOG performance status 0 or 1. 6. Resolution of all acute toxic effects of prior therapy (except for alopecia and neuropathy) or surgical procedure to grade ≤1 or to baseline prior to therapy. 7. Adequate organ function as defined by the following criteria: • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase[SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) ≤2.5 x upper limit of normal (ULN), ≤5 x ULN for patients with liver metastases • Total serum bilirubin ≤1.5 x ULN • Absolute neutrophil count (ANC) ≥1500/µL • Platelets ≥100,000/µL • Hemoglobin ≥9.0 g/dL • Serum creatinine ≤2 x ULN • QTc interval ≤470 msec • Left ventricular ejection fraction (LVEF) ≥lower limit of institutional normal (LLN) as assessed by multigated acquisition (MUGA) scan or echocardiogram (ECHO) 8. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment. 9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of patient reported outcomes questionnaires and an analgesic use diary |
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E.4 | Principal exclusion criteria |
Subjects presenting with any of the following will not be included in the study: 1. Prior treatment with sunitinib (in any clinical setting) and/or more than one prior chemotherapy regimen in the metastatic disease treatment setting. 2. Chemotherapy within 3 weeks of the date of the first dose. 3. Radioisotope therapy with Strontium-89 or Samarium within 12 weeks of the date of the first dose. 4. Radiation therapy (including palliative radiotherapy to metastatic lesion(s)) within 2 weeks or major surgery (e.g., open abdominal, pelvic, thoracic, orthopedic or neurosurgery) within 4 weeks of the date of the first dose. 5. Current treatment on another therapeutic clinical trial. 6. Impending complication from bone metastases (fracture and/or cord compression). Properly treated or stabilized fractures and/or cord compression is allowed. 7. Presence of ongoing urinary obstruction (e.g., urinary retention, hydronephrosis) requiring medical intervention. Properly treated urinary obstruction is allowed. 8. Grade ≥3 hemorrhage within 4 weeks of the date of the first dose. 9. Ongoing cardiac dysrhythmias of grade ≥2. 10. Hypertension that cannot be controlled by medications (>150 mmHg systolic or >100 mmHg diastolic despite optimal medical therapy). 11. Ongoing treatment with therapeutic doses (with therapeutic INR levels) of coumarinderivatives or oral anti-vitamin K agents. 12. Diagnosis of any second malignancy within the last 3 years, except basal cell carcinoma, squamous cell skin cancer, stage I carcinoma fully treated, or in situ carcinoma that have been adequately treated with no evidence of recurrent disease for 12 months. 13. Any of the following within the 6 months prior to study drug administration: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, pulmonary embolism, cerebrovascular accident, or transient ischemic attack. 14. History of, or known brain metastases (skull metastases allowed) and/or carcinomatous meningitis (leptomeningeal disease). 15. Known human immunodeficiency virus (HIV) infection. 16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Patient reported outcomes |
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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 | 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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 108 |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 14 |
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 |
E.8.9.2 | In all countries concerned by the trial days | 14 |