High-risk prostate cancer MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Zytiga
Product Name: abiraterone acetate
Pharmaceutical Form: Tablet
INN or Proposed INN: abiraterone acetate
CAS Number: 154229-18-2
Current Sponsor code: abiraterone acetate
Other descri
Sponsors
Cancer Trials Ireland
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: Each patient must meet all of the following inclusion criteria to be eligible for the study: 1. Provision of written informed consent prior to any study-related procedures 2. Male age = 18 years of age 3. Eastern Cooperative Oncology Group (ECOG) performance status =1 (See Appendix B of the study protocol) 4. Life expectancy = 10 years, as per clinician’s decision Select Ireland - Scroll to ‘expectation of life at age x’ using the most recent indicator for Males) 5. Pathological proven prostate carcinoma at intermediate to high risk of recurrence as defined by RTOG: • Gleason =8; or clinical stage =T3a; or PSA(#) =20 ng/ml(equivalent to AJCC 7th edition 2010 (Edge et al., 2010) / UICC group IIB and III) • Or 2 or more of the following factors: ??Gleason = 7; ??PSA >10 ng/ml but =20 ng/ml, ??T2b-2c (equivalent to AJCC 7th edition 2010 (Edge et al. 2010) / UICC group II) • And planned for radical radiotherapy (External Beam radiation therapy/ Brachytherapy / combination of both) and with an indication for neo-adjuvant hormonal therapy [Note: (#): Study entry PSA must not be obtained during the following time frames: (1) 10-day period following prostate biopsy; (2) following initiation of ADT; (3) within 30 days after discontinuation of finasteride; or (4) within 90 days after discontinuation of dutasteride] 6. Clinically negative lymph nodes (N0) as established by imaging (pelvic CT / MRI), nodal sampling, or dissection within 90 days prior to registration, except patients with lymph nodes equivocal or questionable by imaging are eligible without biopsy if the nodes are =1.5 cm; any node larger than this on imaging will require negative biopsy for eligibility. 7. No evidence of bone metastases (M0) on bone scan within 90 days prior to registration. Equivocal bone scan findings are allowed if plain film x-rays are negative for metastasis. 8. Clinical laboratory values during screening: • Haemoglobin = 10.0 g/dl • Absolute neutrophil count (ANC) = 1.8 × 109/L • Platelets = 100 × 109/L [Note: Study patients need to meet the above 3 criteria independent of growth factors and transfusions] • Total bilirubin = 1.5× upper limit of normal (ULN) • Alanine (ALT) and aspartate (AST) aminotransferase = 2.5 × ULN • Alkaline Phosphatase (ALP) = 6 × ULN • Serum creatinine =1.5 × ULN or creatinine clearance =50 mL/min (Calculated GFR using Cockcroft and Gault Formula) (see Appendix C of the study protocol) • Serum potassium =3.5 mM • Serum albumin =3.0 g/dL • Clinically normal prothrombin (PT) or international normalised ratio (INR) per Investigator assessment 9. Systolic blood pressure =65 years) yes F.1.3.1 Number of subjects for this age range 27
Exclusion criteria
Exclusion criteria: Each patient must meet none of the following exclusion criteria to be eligible for the study: 1. 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: TURP / TRUS is allowed] 2. Use of urethral catheter (in accordance with Ferring CS 30 study - NCT00833248) 3. 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 NYHA Class III or IV heart failure (See Appendix E of the study protocol), or Class II to IV heart failure of cardiac ejection fraction measurement of <50% [cardiac ejection fraction measured by MUGA or ECHO - if indicated, at Investigator’s discretion] 4. Active or symptomatic viral hepatitis, chronic liver disease or severe hepatic impairment 5. 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 procedure to be conducted under local anaesthesia are not excluded from the study] 6. Gastrointestinal disorder interfering with study drug absorption 7. Active or uncontrolled disease that may require oral corticosteroid therapy 8. Positive serology for hepatitis B surface antigen or hepatitis C antibody 9. Known allergies, hypersensitivity or intolerance to abiraterone acetate, prednisolone, GnRH agonists or their excipients 10. Contraindications to the use of prednisolone or GnRH agonists per local prescribing information 11. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study 12. Any condition that, in the opinion of the investigator, would compromise the well-being of the patient or that could prevent, limit, or confound the protocol-specified assessments 13. The patient has or had other co-existing malignancies within the past 5 years, other than resected non-melanoma skin cancer 14. Treatment with non-approved or investigational drug within 30 days before the first planned dose of study drug 15. Treatment with any prohibited medication (as outlined per protocol section 7.4.1) which cannot be discontinued.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: To evaluate the clinical tumour and biochemical response, and 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 naïve high-risk localised prostate carcinoma patients (prior to radical radiotherapy).;Secondary Objective: Secondary Objectives: 1) To report the decrease in testosterone level 2) To report the PSA kinetics and response on the studied treatment 3) To evaluate the potential change in urinary symptoms 4) To report the androgen deprivation-related symptoms and treatment-related toxicities 5) To report the safety profile;Primary end point(s): Primary Efficacy Endpoints: i. Mean reduction in prostatic volume as compared to baseline, by repeated prostate volume measurement by TRUS (prior to treatment and on day 126) (+ / - 3 days) ii. Median change in PSA level after 126 days of study treatment as compared to baseline (prior to treatment, and on day 126) (+/- 3 days) iii. Percentage of patients achieving a complete clinical and biochemical response as defined by a normalisation of digital rectal exam (DRE) and an achieved PSA < 0.1) ;Timepoint(s) of evaluation of this end point: TRUS: 126 days compared to baseline values PSA: 126 days compared to baseline values | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: days 15, 43, 71, 99, and 126 compared to baseline values ;Secondary end point(s): Secondary Efficacy Endpoints: 1) Decrease in testosterone level will be evaluated by serial measurements prior to treatment and on days 15, 43, 71, 99, and 126 (+/- 3 days). 2) The PSA kinetics and response on the studied treatment will be evaluated by serial PSA measurement prior to treatment and on days 15, 43, 71, 99, and 126 (+/- 3 days). 3) The studied treatment impact on urinary symptoms will be evaluated by serial International Prostate Symptom Score (IPSS) prior to treatment and on days 15, 43, 71, 99, and 126 (See Appendix F of the study protocol) (+/- 3 days). Secondary Toxicity/ Safety Endpoints: 1) The potential toxicity of the studied treatment will be evaluated by: i. NCI CTCAE Version 4.0 Grading system for Androgen deprivation-related symptoms (See Appendix D of the study protocol) ii. Serial IIEF scores for erectile dysfunction prior to treatment and on days 15, 43, 71, 99, and 126 (See Appendix G of the study protocol) (+/- 3 days) 2) The safety of the studied treatment will be evaluated by: i. Frequency and grade of AEs (Grade = 4 toxicity event) ii. Clinically relevant changes in laboratory values | — |
Countries
Ireland
Contacts
Public ContactHead of Clinical Operations
Cancer Trials Ireland
Outcome results
None listed