NCT02077634CompletedPhase 2
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)
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Universität des Saarlandes
- Enrollment
- 68
- Locations
- 20
- Primary Endpoint
- radiographic-progression-free survival
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
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 7)
- •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
- •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
- •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.
Arms & Interventions
abiraterone acetate + prednisone + LHRH-therapy
Active Comparator
Patients randomized to this group will continue their LHRH-therapy.
Intervention: abiraterone acetate + prednisone + LHRH-therapy (Drug)
abiraterone acetate + prednisone
Active Comparator
Patients randomized to this group will stop LHRH-therapy.
Intervention: abiraterone acetate + prednisone (Drug)
Outcomes
Primary Outcomes
radiographic-progression-free survival
Time Frame: 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 Outcomes
- Correlation of radiographic-progression-free survival with early PSA-response(12 month)
- Hormonal analyses(12 month)
- Adverse Events(12 month)
Investigators
Study Sites (20)
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