Phase II Single-arm Study Evaluating Neo-adjuvant (Pre-radical Radiotherapy) Abiraterone Acetate (Plus Prednisolone) and Gonadotropin-Releasing Hormone (GnRH) Agonist in High Risk Localised Prostate Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Abiraterone acetate, Prednisolone
- Conditions
- High Risk Localised Prostate Carcinoma
- Sponsor
- Cancer Trials Ireland
- Enrollment
- 45
- Locations
- 4
- Primary Endpoint
- Biochemical response
- Status
- Completed
- Last Updated
- 19 days ago
Overview
Brief Summary
The role of this study is to focus on the potential role of abiraterone acetate in treatment-naive patients newly diagnosed with high-risk localised prostate cancer requiring combined hormonal therapy and radiotherapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Provision of written informed consent prior to any study related procedures
- •Males aged 18 years or older
- •ECOG performance status of less than or equal to 1
- •Life expectancy of 10 years or more (using MSKCC nomogram)
- •Pathological proven prostate carcinoma at intermediate to high risk of recurrence as defined by RTOG
- •Clinically negative lymph nodes as established by imaging (pelvic CT / MRI), nodal sampling, or dissection within 60 days prior to registration, except patients with lymph nodes equivocal or questionable by imaging are eligible without biopsy if the nodes are less than or equal to 1.5cm; any node larger than this ion imaging will require negative biopsy for eligibility
- •No evidence of bone metastases on bone scan within 60 days prior to registration. Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis.
- •Clinical laboratory values during screening:
- •Haemoglobin greater than or equal to 10.0g/dl
- •Absolute neutrophil count (ANC) ≥ 1.8 × 10 to the power of 9/L
Exclusion Criteria
- •Prior treatment for prostate carcinoma, including prostatectomy; high intensity focused ultrasound or cryotherapy; hormonal manipulation (any modalities) including LHRH agonist, anti-androgen, or bilateral orchidectomy; prior or concomitant chemotherapy for prostate cancer; prior radiotherapy including brachytherapy to the region of study cancer; radical local treatment \[Exception: Transuretheral Resection of the Prostate (TRUP) / TRUS is allowed\]
- •Use of urethral catheter
- •History of cardiovascular disease; Uncontrolled hypertension \[hypertension controlled by anti-hypertensive therapy is permitted\], clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart failure, or Class II to IV heart failure of cardiac ejection fraction measurement of \<50%
- •Active or symptomatic viral hepatitis or chronic liver disease
- •Major thoracic or abdominal surgery or significant traumatic injury within 4 weeks prior to registration, or planned surgery during study participation / within 4 weeks from end of treatment \[Note: patients with planned surgical procedures to be conducted under local anaesthesia are not excluded from the study\]
- •Gastrointestinal disorder interfering with study drug absorption
- •Active or uncontrolled disease that may require oral corticosteroid therapy
- •Positive serology for hepatitis B surface antigen or hepatitis C antibody
- •Known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisolone, GnRH agonists or their excipients
- •Contraindications to the use of prednisolone or GnRH agonists per local prescribing information
Arms & Interventions
Combined hormonal therapy
Abiraterone acetate: 1000mg/day (four 250g tablets, orally once a day) for 126 days Prednisolone; 5mg/day (1 tablet orally once a day, concomitant to abiraterone acetate) for 126 days GnRh agonist for 4 injections (at 28 day intervals)
Intervention: Abiraterone acetate, Prednisolone
Outcomes
Primary Outcomes
Biochemical response
Time Frame: 126 days
To evaluate biochemical response achieved by 126 days of neo-adjuvant combined treatment by abiraterone acetate, prednisolone and GnRH agonist - in treatment naive high-risk localised prostate carcinoma patients (prior to radical radiotherapy)
Clinical tumour response
Time Frame: 126 days
To evaluate the clinical tumour response achieved by 126 days of neo-adjuvant combined treatment by abiraterone acetate, prednisolone and GnRH agonist in treatment of naive high-risk localised prostate carcinoma patients (prior to radical radiotherapy)
Mean percentage reduction in prostate gland volume
Time Frame: 126 days
To evaluate the mean percentage reduction in prostate gland volume achieved by 126 days of neo-adjuvant combined treatment by abiraterone acetate, prednisolone and GnRH agonist - in treatment naive high-risk localised prostate carcinoma patients (prior to radical radiotherapy)
Secondary Outcomes
- Testosterone level(126 days)