E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hormone refractory prostate cancer |
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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 |
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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 the anti-tumor effects of CB7630 in patients with androgen independent metastatic prostate cancer (AIPC) who have failed docetaxel based chemotherapy, as measured by the proportion of patients achieving a PSA decline of >50% (PSA response) according to Prostate-Specific Antigen Working Group (PSAWG) criteria
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E.2.2 | Secondary objectives of the trial |
• To assess the rate of objective response in patients with measurable lesions by RECIST criteria • To determine the duration of PSA decline, and objective response if applicable • To determine the duration of progression-free survival • To determine the safety and tolerability of CB7630 in study population • To assess clinical benefits as determined by symptomatic relief, disease stabilization, and improvement of performance status • To evaluate the role of circulating tumor cell (CTC) enumeration and isolation in the assessment of prognosis and treatment response in study population. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to provide written informed consent 2. Written Authorization for Use and Release of Health and Research Study Information (USA sites only) or Data Protection Consent (European sites only) has been obtained 3. Age ≥ 18 years and male 4. Histologically or cytologically confirmed adenocarcinoma of the prostate, but not with neuroendocrine differentiation or of small cell histology. 5. Prior chemotherapy for prostate cancer with regimen(s) containing paclitaxel or docetaxel. 6. Documented PSA progression according to PSAWG eligibility criteria with a PSA> 5 ng/mL. 7. On-going androgen deprivation with serum testosterone < 50 ng/dL (< 2.0nM) 8. Serum potassium ≥ 3.5 mmol/L 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2 (Karnofsky Performance Status ≥ 50%) 10. No history of adrenal insufficiency or hyperaldosteronism 11. Any acute toxicities of prior chemotherapy, radiotherapy have resolved to a NCI CTCAE (version 3) grade of ≤ 1. Chemotherapy induced alopecia and grade 2 neuropathy are excluded from this consideration. 12. No radiotherapy, chemotherapy or immunotherapy within 30 days of administration of the Cycle 1 Day 1. Supportive care with glucocorticoid is not considered as an immunotherapy; however, PSA progression must be documented under current dose/regimen 13. No surgery or local prostatic intervention within 28 days of the first dose. In addition, any clinically relevant sequelae from the surgery must have resolve prior to Cycle 1 Day 1. 14. Life expectancy > 12 weeks 15. Able to swallow the CB7630 whole as a capsule 16. Able to follow study instructions, accessible for treatment and follow-up, and likely to complete all study requirements.
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E.4 | Principal exclusion criteria |
1. Active or uncontrolled autoimmune disease that may require corticosteroid therapy 2. Serious or uncontrolled co-existent non-malignant disease, including active and uncontrolled infection. 3. Uncontrolled hypertension 4. Hemoglobin ≤ 9.0 g/dL 5. Abnormal liver function tests consisting of any of the following: • Serum bilirubin > 1.5 x ULN • ALT > 2.5 x ULN • AST > 2.5 x ULN 6. Serum creatinine > 2.0 x UNL or a calculated creatinine clearance < 50 mL/min 7. Clinically significant heart disease as evidenced by a myocardial infarction in the past twelve months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease. Patients with a history of atherosclerotic vascular disease requiring coronary or peripheral artery bypass surgery may be enrolled provided the surgery occurred at least two years prior to enrollment and after consultation with a cardiologist to insure that the disease is stable. 8. Other malignancy within the previous 5-years other than basal cell or squamous cell carcinomas of skin with a > 30% probability of recurrence within 12 months. 9. History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study medication. 10. Current enrollment in an investigational drug or device study or participation in such a study within 30 days of Cycle 1 Day 1 11. Condition or situation which, in the investigator’s opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient’s participation in the study. 12. Patients who have partners of childbearing potential who are not willing to use a method of birth control with adequate barrier protection as determined to be acceptable by the principal investigator and sponsor during the study and for 13 weeks after last study drug administration
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E.5 End points |
E.5.1 | Primary end point(s) |
Serum PSA decline according to Prostate-Specific Antigen Working Group (PSAWG) criteria. Other efficacy measures include tumor response in patients with measurable lesions based on RECIST criteria; the duration of PSA decline by > 50% and objective response (if applicable); duration of progression-free survival; and clinical benefit as determined by symptomatic relief, disease stabilization, and improvement of performance status. Safety endpoints include incidence of worst grade adverse events; incidence of deaths and other serious and significant adverse events; and incidence of worst grade laboratory abnormalities.
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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 | Yes |
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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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 | No |
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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Completion of dosing with 12 Cycles of treatment with arbiraterone acetate or early termination. If the final patient has an ongoing AE related to protocol treatment, the trial will end when the AE is resolved.
Patients benefiting from treatment will be offered the opportunity to continue treatment with CB7630 in a separate study at the end of Cycle 12.
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |