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 | 8.0 |
E.1.2 | Classification code | 10062904 |
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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 safety, tolerability and recommended dose of abiraterone acetate administered orally, by continuous once-daily administration in patients with HRPC.
To determine the effect of abiraterone acetate on the pituitary-adrenal-gonad endocrine axis and on adrenal hormones by evaluating serum levels of testosterone and its precursors.
To evaluate the efficacy of abiraterone acetate in HRPC at recommended dose. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the pharmacokinetic profile of abiraterone acetate.
To estimate duration of PSA/objective tumour response.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Age >18 years and able to comply with protocol requirements. 2) Signed informed consent. 3) Histologically documented adenocarcinoma of the prostate, clinically refractory or resistant to hormone therapy, as documented by progression following at least one hormonal therapy, which must include orchiectomy or ongoing treatment with gonadotropin releasing hormone (GnRH) agonists. 4) PSA evidence for progressive prostate cancer consists of a PSA level of at least 5 ng/ml which has risen on at least 2 successive occasions, at least 2 weeks apart. If the confirmatory PSA value is less than the screening PSA value, then an additional test for rising PSA will be required to document progression. 5) Patients who were withdrawn from anti-androgen therapy less than 6 months prior to inclusion in the study require one PSA higher than the last pre-withdrawal PSA or 2 increases in PSA documented after the post-withdrawal nadir ≥ 4 weeks from treatment withdrawal if treated with flutamide and ≥6 weeks if treated with bicalutamide or nilutamide. Patients with progression of measurable disease (RECIST) or progression of bone disease must also fit the criterion for PSA progression. 6) ECOG performance status: 0-1. 7) Creatinine ≤1.5 x upper limit of normal (ULN) or a calculated creatinine clearance > 50 mL/min. 8) Potassium ≥ 3.5mmol/l. 9) Systolic blood pressure < 160 and diastolic < 100 mmHg documented on at least 3 different days. 10) Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients who have not had an orchiectomy, must be maintained on effective LHRH analogue therapy before and during the trial. 11) Castrate testosterone level [< 50 ng/dL or < 2.00 nmol/L (nmol/L x 28.8 = ng/dL)]. 12) Normal baseline ACTH stimulation test. The criterion will be removed if no evidence of adrenocortical insufficiency is observed in the dose escalation phase. 13) Life expectancy of ≥ 12 weeks.
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E.4 | Principal exclusion criteria |
1) Prior cytotoxic chemotherapy for prostate cancer (including estramustine, docetaxel and mitoxantrone). All other systemic chemotherapy must have been completed at least 2 years prior to enrolment. 2) Prior therapeutic radionucleotide therapy for prostate cancer. 3) External beam radiotherapy, brachytherapy or cryotherapy to the prostate bed within 4 weeks of start of study. 4) Prior ketoconazole, aminoglutethimide or treatment with any investigational anticancer agent, including systemic corticosteroids for the treatment of prostate cancer, within 4 weeks of start of study. 5) Patients receiving any other hormonal therapy, including any dose of megestrol acetate (Megace), Proscar (finasteride), any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES), or any systemic corticosteroid must discontinue the agent for at least 4 weeks prior to enrolment. Progressive disease (as defined above) must be documented after discontinuation of the hormonal therapy. 6) Treatment with any investigational anticancer agent within 4 weeks of start of study. 7) Patients on stable doses of bisphosphonates that show subsequent tumour progression may continue on this medication; however, patients are not allowed to initiate bisphosphonate therapy within two weeks prior to starting therapy or throughout the study. 8) No supplements or complementary medicines/botanicals are permitted while on protocol therapy, except for any combination of the following: • conventional multivitamin supplements • selenium • soy supplements 9) Haemoglobin ≤ 9.0 g/dL, ANC ≤ 1.5 x 10 to the power of 9 /L, platelets ≤100 x 10 to the power of 9/L. 10) Bilirubin > 1.5 x ULN, AST >2.5 x ULN, ALT > 2.5 x ULN. 11) Patients with serious or uncontrolled co-existent non-malignant diseases. Active or uncontrolled infection. 12) Patients with CNS disease and/or brain metastases. 13) No “currently active” second malignancy, other than non-melanoma skin cancer. Patients are not considered to have a "currently active” malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse. 14) Clinical and/or biochemical evidence of hyperaldosteronism. 15) Patients with well controlled hypertension with medication will be allowed after the dose escalation study is completed. 16) NYHA Class III or IV Congestive Heart Failure. 17) Myocardial infarction within the 6 months prior to start of study. 18) No active or uncontrolled autoimmune disease that may require corticosteroid therapy during protocol treatment. 19)Major surgery or significant traumatic injury within 4 weeks of start of study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Confirmed, objective PSA response (according to PSAWG criteria) resulting from abiraterone acetate therapy. All patients achieving a fall in PSA of >50% from baseline, which has been confirmed by a second measurement at least 4 weeks after initial documentation, will fulfill criteria for PSA response. Baseline measurements should be within three days of starting study therapy. Patients achieving a fall of their PSA to less than 0.2ng/ml will be reported as a subset of PSA responders. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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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The final follow up (assessment) visit of the final patient will be at least 30 days following the last dose of abiratone acetate. If the final patient has an ongoing adverse event related to protocol treatment, the trial will end when the adverse event is resolved.
Patients who are maintaining a response to therapy or who have stable disease at the end of the formal study period may be offered the opportunity to continue Abiraterone acetate treatment under a separate protocol. |
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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 | |