Medically castrated male patients with chemotherapy-naïve, castration-resistant, metastatic CRPC who have shown tumor progression and are non- or mildly-symptomatic MedDRA version: 16.1 Level: LLT Classification code 10066489 Term: Progression of prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Zytiga
Product Name: Abiraterone Acetate
Product Code: JNJ 212082
Pharmaceutical Form: Tablet
CAS Number: 154229-18-2
Other descriptive name: ABIRATERONE ACETATE
Concentration unit: mg mil
Sponsors
Universität des Saarlandes
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Willing and able to provide written informed consent 2. Written Data Protection Consent has been obtained 3. Male aged 18 years and above 4. Histologically or cytologically confirmed adenocarcinoma of the prostate 5. Metastatic disease documented by positive bone scan or metastatic lesions other than liver or visceral metastasis on CT, MRI. If lymph node metastasis is the only evidence of metastasis, it must be =2 cm in diameter 6. Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria 7. Asymptomatic or mildly symptomatic from prostate cancer. A score of 0-1 for the question of worst pain within last 24 hours (Appendix 8) will be considered asymptomatic, and a score of 2-3 will be considered mildly symptomatic. 8. Medically castrated, with testosterone levels of =65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: 1. Surgical castration (i.e. orchiectomy). 2. Application of any LHRH-therapy (LHRH-analogue or LHRH-antagonist) within 3 months (for patients receiving a 3-months formulation) or 1 months (for patients receiving a 1-month formulation) prior to Cycle 1 day 1. 3. Patients receiving a 6- or 12-months formulation of LHRH-therapy 4. Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated 5. Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone/prednisolone bid. 6. Pathological finding consistent with small cell carcinoma of the prostate 7. Liver or visceral organ metastasis 8. Known brain metastasis 9. Use of opiate analgesics for cancer-related pain, including codeine, tramadol, tilidin and others (see Appendix 9), currently or anytime within 4 weeks of Cycle 1 Day 1. 10. Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC 11. Radiation therapy for treatment of the primary tumour within 6 weeks of Cycle 1, Day 1 12. Radiation or radionuclide therapy for treatment of metastatic CRPC 13. Prior treatment with Abiraterone acetate or other CYP17 inhibitors (ketoconazole, TAK700, TOK001) or investigational agents targeting the androgen receptor for prostate cancer for more than 7 days 14. Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1 15. Prior flutamide (Eulexin) treatment within 4 weeks of Cycle 1, Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1) 16. Bicalutamide (Casodex), nilutamide (Nilandron) within 6 weeks of Cycle 1 Day 1 (patients whose PSA did not decline for three or more months in response to antiandrogen given as a second line or later intervention will require only a two week washout prior to Cycle 1, Day 1) 17. Uncontrolled hypertension (systolic BP =160 mmHg or diastolic BP =95 mmHg). Patients with a history of hypertension are allowed provided that blood pressure is controlled by anti-hypertensive treatment 18. Active or symptomatic viral hepatitis or chronic liver disease 19. History of pituitary or adrenal dysfunction 20. 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 (NYHA) Class II-IV heart disease or cardiac ejection fraction measurement of <50 % at baseline 21. Any condition that requires treatment with Digoxin, digitoxin, and other digitalis drugs 22. Atrial Fibrillation, or other cardiac arrhythmia requiring therapy 23. Other malignancy with a =30 % probability of recurrence within 24 months, except non-melanoma skin cancer. 24. Administration of an investigational therapy within 30 days of Cycle 1, Day 1 25. Any condition, which, in the opinion of the investigator, would preclude participation in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to analyze the clinical benefit of abiraterone acetate plus prednisone while adding or sparing LHRH-therapy in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (CRPC).;Secondary Objective: To establish additional clinically relevant information regarding early PSA responses to abiraterone and to correlate these with radiographic-progression free survival To investigate effects of both treatment arms on hormones of the pituitary gonadal axis To characterize the safety profile of abiraterone acetate while sparing LHRH-therapy in comparison to continuing LHRH-therapy ;Primary end point(s): Primary endpoint of the study is rate of radiographic progression-free survival (rPFS) at month 12 based on parameters suggested by PCWG2 and modified RECIST as the time from randomization to the occurrence of one of the following: 1.A patient is considered to have progressed by bone scan if: a. The first bone scan with =2 new lesions compared to baseline is observed <12 weeks from randomization and is confirmed by a second bone scan taken =6 weeks later shown =2 additional new lesions (a total of =4 lesions compared to baseline); b. The first bone scan with =2 new lesions compared to baseline is observed =12 weeks from randomization and the new lesions are verified on the next bone scan =6 weeks later (a total of =2 new lesions compared to baseline). 2. Progression of soft tissue lesions measured by CT or MRI as defined in modified RECIST criteria. 3. Death from any cause ;Timepoint(s) of evaluation of this end point: After 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PSA response rate scored in patients achieving a post-treatment PSA decline of at least 50% according to the protocol-specific PCWG2 criteria Time to PSA-progression will be measured from the time interval from the date of randomization to the date of the PSA progression as defined in the protocol-specific PCWG2 criteria. The determination of PSA progression will require that the patient receive at least 3 cycles of therapy. Objective response rate in patients with measurable disease (RECIST) Changes in pituitary gonadal axis by measurement of androgens and hormones (LHRH, LH, FSH, testosterone, DHT);Timepoint(s) of evaluation of this end point: After 12 months | — |
Countries
Germany
Contacts
Public ContactHeidrun Rexer
MeckEvidence
Outcome results
None listed