Trial of Abiraterone Acetate Plus LHRH-therapy Versus Abiraterone Acetate Sparing LHRH-therapy in Patients With Progressive Chemotherapy-naïve Castration-resistant Prostate Cancer (SPARE)

Prostate Cancer Clinical Trial

— SPARE  

Official title:

Randomized Phase-II Trial of Abiraterone Acetate Plus LHRH-therapy Versus Abiraterone Acetate Sparing LHRH-therapy in Patients With Progressive Chemotherapy-naïve Castration-resistant Prostate Cancer (SPARE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02077634
• Other study ID #: SPARE-001
• Secondary ID: AUO study number
• Status: Completed
• Phase: Phase 2
• Start date: May 2014
• Est. completion date: April 1, 2019

Study information

• Verified date: March 2020
• Source: Saarland University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: April 1, 2019
• Est. primary completion date: April 1, 2019
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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 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

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 <20-50 ng/dl (< 2.0 nM).

9. 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).

10. Eastern Cooperative Oncology Group (ECOG) Performance Status of =2 (Appendix 6)

11. Hemoglobin =9.0 g/dL independent of transfusion

12. Platelet count =100,000 /µl

13. Serum albumin =3.0 g/dl

14. Serum creatinine < 1.5 x ULN or a calculated creatinine clearance =60 ml/min (Appendix 7)

15. Serum potassium =3.5 mmol/l

16. Liver function:

1. Serum bilirubin <1.5 x ULN (except for patients with documented Gilbert's disease)

2. AST or ALT <2.5 x ULN

17. Able to swallow the study drug whole as a tablet

18. Life expectancy of at least 6 months

19. 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:

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 5mg 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) ), Enzalutamide (Xtandi) 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, Day1)

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.

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• abiraterone acetate + prednisone + LHRH-therapy
Hormon therapy will go on
• abiraterone acetate + prednisone
ormon therapy will be stopped

Locations

Country	Name	City	State
Germany	Gemeinschaftspraxis für Onkologie	Augsburg
Germany	Gemeinschaftspraxis für Urologie	Berlin
Germany	Urologie Bonn-Rhein-Sieg, Praxis Bad Godesberg	Bonn
Germany	Praxisgemeinschaft für Urologie	Borken
Germany	Urologicum Duisburg	Duisburg
Germany	Urologicum Hamburg	Hamburg
Germany	Universitätsklinikum Homburg/Saar, Klinik für Urologie und Kinderurologie	Homburg/Saar
Germany	Urologische Gemeinschaftspraxis	Kempen
Germany	Facharztpraxis Dr. Klier, Cologne-Study-Group	Köln
Germany	Klinikum Landshut	Landshut
Germany	Urologisches Zentrum Lübeck (UZL)	Lübeck
Germany	Gemeinschaftspraxis PUR-R	Mülheim/Ruhr
Germany	Gemeinschaftspraxis Urologie Pasing	München
Germany	Privatärztliche urologische Studienpraxis	Nürtingen
Germany	Pandamed - Übag	Remscheid
Germany	Zentrum für Onkologie und Urologie Rostock, Wissenschaftskontor Nord GmbH & Co. KG	Rostock
Germany	Praxisgemeinschaft für Onkologie und Urologie	Wilhelmshaven
Germany	Praxisgemeinschaft	Wolfsburg
Germany	DGU	Wuppertal
Germany	Pandamed - Übag	Wuppertal
Germany	Praxis für Urologie	Würselen
Germany	Praxis für Urologie	Zwickau

Sponsors (1)

Lead Sponsor	Collaborator
Saarland University

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	radiographic-progression-free survival	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).	12 month
Secondary	Correlation of radiographic-progression-free survival with early PSA-response	To establish additional clinically relevant information regarding early PSA responses to abiraterone and to correlate these with radiographic-progression free survival	12 month
Secondary	Hormonal analyses	To investigate effects of both treatment arms on hormones of the pituitary gonadal axis	12 month
Secondary	Adverse Events	To characterize the safety profile of abiraterone acetate while sparing LHRH-therapy in comparison to continuing LHRH-therapy	12 month