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

NCT ID: NCT02077634

Last Updated: 2020-03-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2019-04-01

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

abiraterone acetate + prednisone + LHRH-therapy

Patients randomized to this group will continue their LHRH-therapy.

Group Type: ACTIVE_COMPARATOR

abiraterone acetate + prednisone + LHRH-therapy

Intervention Type: DRUG

Hormon therapy will go on

abiraterone acetate + prednisone

Patients randomized to this group will stop LHRH-therapy.

Group Type: ACTIVE_COMPARATOR

abiraterone acetate + prednisone

Intervention Type: DRUG

ormon therapy will be stopped

Interventions

abiraterone acetate + prednisone + LHRH-therapy

Hormon therapy will go on

Intervention Type: DRUG

abiraterone acetate + prednisone

ormon therapy will be stopped

Intervention Type: DRUG

Eligibility 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 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Universität des Saarlandes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carsten-Henning Ohlmann, PD Dr.

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Saarland

Locations

Gemeinschaftspraxis für Onkologie

Augsburg, , Germany

Gemeinschaftspraxis für Urologie

Berlin, , Germany

Urologie Bonn-Rhein-Sieg, Praxis Bad Godesberg

Bonn, , Germany

Praxisgemeinschaft für Urologie

Borken, , Germany

Facharztpraxis Dr. Klier, Cologne-Study-Group

Cologne, , Germany

Urologicum Duisburg

Duisburg, , Germany

Urologicum Hamburg

Hamburg, , Germany

Universitätsklinikum Homburg/Saar, Klinik für Urologie und Kinderurologie

Homburg/Saar, , Germany

Urologische Gemeinschaftspraxis

Kempen, , Germany

Klinikum Landshut

Landshut, , Germany

Urologisches Zentrum Lübeck (UZL)

Lübeck, , Germany

Gemeinschaftspraxis PUR-R

Mülheim, , 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, , Germany

Countries

Germany

References

Ohlmann CH, Jaschke M, Jaehnig P, Krege S, Gschwend J, Rexer H, Stockle M. Abiraterone acetate plus LHRH therapy versus abiraterone acetate while sparing LHRH therapy in patients with progressive, metastatic and chemotherapy-naive, castration-resistant prostate cancer (SPARE): study protocol for a randomized controlled trial. Trials. 2017 Oct 4;18(1):457. doi: 10.1186/s13063-017-2195-x.

Reference Type: DERIVED

PMID: 28978327 (View on PubMed)

Other Identifiers

AUO study number

Identifier Type: OTHER

Identifier Source: secondary_id

SPARE-001

Identifier Type: -

Identifier Source: org_study_id