Trial of Abiraterone Acetate Plus LHRH-therapy Versus Abiraterone Acetate Sparing LHRH-therapy in Patients With Progressive Chemotherapy-naïve Castration-resistant Prostate Cancer (SPARE)
Study Details
Study Description
Brief Summary
This is an exploratory Phase 2 multicenter, randomized, open-label study with a randomization allocation ratio of 1:1 [abiraterone acetate + prednisone + LHRH-therapy (Arm A) versus abiraterone acetate + prednisone (Arm B)]. For both groups patients will receive a dose of 1000 mg abiraterone acetate and 10mg prednisone daily (QD). Study drug will be administered as 4 x 250-mg abiraterone acetate tablets and prednisone will be administered as 5 mg orally twice a day (BID). Patients randomized to the LHRH-therapy group will receive the same LHRH-therapy they received prior to entering the trial. 70 medically castrated male patients with metastatic CRPC who have shown tumor progression and are non- or mildly-symptomatic will be enrolled from approximately 12 German study sites.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: abiraterone acetate + prednisone + LHRH-therapy Patients randomized to this group will continue their LHRH-therapy. |
Drug: abiraterone acetate + prednisone + LHRH-therapy
Hormon therapy will go on
|
| Active Comparator: abiraterone acetate + prednisone Patients randomized to this group will stop LHRH-therapy. |
Drug: abiraterone acetate + prednisone
ormon therapy will be stopped
|
Outcome Measures
Primary Outcome Measures
- radiographic-progression-free survival [12 month]
The primary objective of the study is to analyze the clinical benefit of abiraterone acetate plus prednisone while sparing LHRH-therapy in chemotherapy-naïve patients with metastatic castration-resistant prostate cancer (CRPC).
Secondary Outcome Measures
- Correlation of radiographic-progression-free survival with early PSA-response [12 month]
To establish additional clinically relevant information regarding early PSA responses to abiraterone and to correlate these with radiographic-progression free survival
- Hormonal analyses [12 month]
To investigate effects of both treatment arms on hormones of the pituitary gonadal axis
- Adverse Events [12 month]
To characterize the safety profile of abiraterone acetate while sparing LHRH-therapy in comparison to continuing LHRH-therapy
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing and able to provide written informed consent
-
Written Data Protection Consent has been obtained
-
Male aged 18 years and above
-
Histologically or cytologically confirmed adenocarcinoma of the prostate
-
Metastatic disease documented by positive CT/MRI and/or bone scan (both must be performed). If lymph node metastasis is the only evidence of metastasis, it must be ≥2 cm in diameter
-
Prostate cancer progression documented by PSA according to PCWG2 or radiographic progression according to modified RECIST criteria
-
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.
-
Medically castrated, with testosterone levels of <20-50 ng/dl (< 2.0 nM).
-
Combined androgen blockade is permitted, but not required. If patients received combined androgen blockade with an anti-androgen they must have shown PSA progression after discontinuing the anti-androgen prior to enrollment (≥4 weeks since last flutamide, ≥6 weeks since last bicalutamide or nilutamide).
-
Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤2 (Appendix 6)
-
Hemoglobin ≥9.0 g/dL independent of transfusion
-
Platelet count ≥100,000 /μl
-
Serum albumin ≥3.0 g/dl
-
Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥60 ml/min (Appendix
-
Serum potassium ≥3.5 mmol/l
-
Liver function:
-
Serum bilirubin <1.5 x ULN (except for patients with documented Gilbert's disease)
-
AST or ALT <2.5 x ULN
-
Able to swallow the study drug whole as a tablet
-
Life expectancy of at least 6 months
-
Patients who have partners of childbearing potential must be 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 1 week after last study drug administration.
Exclusion Criteria:
-
Surgical castration (i.e. orchiectomy).
-
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.
-
Patients receiving a 6- or 12-months formulation of LHRH-therapy
-
Active infection or other medical condition that would make prednisone/prednisolone (corticosteroid) use contraindicated
-
Any chronic medical condition requiring a higher dose of corticosteroid than 5mg prednisone/prednisolone bid.
-
Pathological finding consistent with small cell carcinoma of the prostate
-
Liver or visceral organ metastasis
-
Known brain metastasis
-
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.
-
Prior cytotoxic chemotherapy or biologic therapy for the treatment of CRPC
-
Radiation therapy for treatment of the primary tumour within 6 weeks of Cycle 1, Day 1
-
Radiation or radionuclide therapy for treatment of metastatic CRPC
-
Prior treatment with Abiraterone acetate or other CYP17 inhibitors (ketoconazole, TAK700, TOK001) ), Enzalutamide (Xtandi) or investigational agents targeting the androgen receptor for prostate cancer for more than 7 days
-
Prior systemic treatment with an azole drug (e.g. fluconazole, itraconazole) within 4 weeks of Cycle 1, Day 1
-
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)
-
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, Day1)
-
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
-
Active or symptomatic viral hepatitis or chronic liver disease
-
History of pituitary or adrenal dysfunction
-
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
-
Any condition that requires treatment with Digoxin, digitoxin, and other digitalis drugs
-
Atrial Fibrillation, or other cardiac arrhythmia requiring therapy
-
Other malignancy with a ≥30 % probability of recurrence within 24 months, except non- melanoma skin cancer.
-
Administration of an investigational therapy within 30 days of Cycle 1, Day 1
-
Any condition, which, in the opinion of the investigator, would preclude participation in this trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Gemeinschaftspraxis für Onkologie | Augsburg | Germany | 86150 | |
| 2 | Gemeinschaftspraxis für Urologie | Berlin | Germany | 13187 | |
| 3 | Urologie Bonn-Rhein-Sieg, Praxis Bad Godesberg | Bonn | Germany | 53177 | |
| 4 | Praxisgemeinschaft für Urologie | Borken | Germany | 46325 | |
| 5 | Urologicum Duisburg | Duisburg | Germany | 47179 | |
| 6 | Urologicum Hamburg | Hamburg | Germany | 22399 | |
| 7 | Universitätsklinikum Homburg/Saar, Klinik für Urologie und Kinderurologie | Homburg/Saar | Germany | 66421 | |
| 8 | Urologische Gemeinschaftspraxis | Kempen | Germany | 47906 | |
| 9 | Facharztpraxis Dr. Klier, Cologne-Study-Group | Köln | Germany | 50968 | |
| 10 | Klinikum Landshut | Landshut | Germany | 84034 | |
| 11 | Urologisches Zentrum Lübeck (UZL) | Lübeck | Germany | 23560 | |
| 12 | Gemeinschaftspraxis PUR-R | Mülheim/Ruhr | Germany | 45468 | |
| 13 | Gemeinschaftspraxis Urologie Pasing | München | Germany | 81241 | |
| 14 | Privatärztliche urologische Studienpraxis | Nürtingen | Germany | 72622 | |
| 15 | Pandamed - Übag | Remscheid | Germany | 42853 | |
| 16 | Zentrum für Onkologie und Urologie Rostock, Wissenschaftskontor Nord GmbH & Co. KG | Rostock | Germany | 18107 | |
| 17 | Praxisgemeinschaft für Onkologie und Urologie | Wilhelmshaven | Germany | 26389 | |
| 18 | Praxisgemeinschaft | Wolfsburg | Germany | 38440 | |
| 19 | DGU | Wuppertal | Germany | 42103 | |
| 20 | Pandamed - Übag | Wuppertal | Germany | 42103 | |
| 21 | Praxis für Urologie | Würselen | Germany | 52146 | |
| 22 | Praxis für Urologie | Zwickau | Germany | 08060 |
Sponsors and Collaborators
- Universität des Saarlandes
Investigators
- Principal Investigator: Carsten-Henning Ohlmann, PD Dr., University Hospital, Saarland
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SPARE-001
- AUO study number