Abiraterone-Rechallenge Study for CRPC Patients

Study Overview
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Brief Summary
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To assess activity of abiraterone-re-challenge in patients with advanced prostate cancer and prior response to abiraterone.

Detailed Description
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To assess activity of abiraterone-re-challenge in patients with advanced prostate cancer and prior response to abiraterone. CRPC patients with prior response to abiraterone (confirmed PSA Response) and progression can be re-challenged with abiraterone. Patients may have received treatment with docetaxel, enzalutamide and radium-223.

Official Title
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An Open Label Biomarker Driven Phase II Clinical Trial of Abiraterone Acetate (AA) Re-Challenge in Patients With Metastatic Castration-Resistant Prostate Cancer and Prior Response to AA

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: abiraterone acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written prostate cancer. Adult patients with histological or cytological diagnosis of adenocarcinoma of the prostate. Men with castration-resistant metastatic decline maintained for at least 3 weeks as per PCWG2 criteria). Confirmed biochemical response to prior abiraterone acetate (≥50% PSA Informed Consent (including consent for biomarker studies including the fresh tumour biopsies) Progressive disease according to PCWG2 criteria during prior therapy with standard dose of abiraterone acetate (confirmed increase of PSA ≥25% over nadir) or soft-tissue or bone progression. Patients that have stopped abiraterone acetate for reasons other than progression are not eligible. Documented progression of disease by any of the criteria listed here: PSA Soft tissue Bone scan all as per PCWG2 criteria Patients may have received treatment with docetaxel, enzalutamide or radium-223 PSA of ≥10ug/l ECOG performance status 0 - 2 At least 3 months (90 days) since stop of prior abiraterone acetate. Exclusion Criteria: Major surgery within 28 days weeks prior to start of treatment Prior treatment with cabazitaxel or the CYP-17 inhibitor TAK-700/orteronel Any concurrent treatment or prior treatment with an investigational drug within 28 days prior to start of treatment. Known brain or leptomeningeal disease Concurrent use of steroids other than prednisone >10mg/d Inadequate bone marrow and organ function as evidenced by: Platelet count <75 x 10 G/L ASAT and/or ALAT ≥ 2.5 x ULN Total bilirubin ≥ 1.5 x ULN (≥ 2.0 x ULN for patients with Gilbert's disease) Hypokalaemia despite adequate supplementation Creatinine Clearance <30ml/min Uncontrolled hypertension or cardiac failure or LVEF <50% creatinine clearance is to be calculated by using the formula of Cockcroft-Gault in appendix 4 of the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone<br>Abiraterone acetate 1000 mg once daily and Prednisone 2x5 mg daily (continuously as per prescription label). | Drug: abiraterone acetate<br>* Abiraterone acetate 1000 mg once daily and Prednisone 2x5 mg daily (continuously as per prescription label).<br>* Other names: Zytiga;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Soft-tissue and PSA Response per PCWG2 | at week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of CTC conversion | Rate of CTC conversion from a baseline count of ≥5/7.5ml to <5/7.5ml | Measured at baseline and at 12 weeks | 
| Rate of PSA decline 30% | Rate of PSA declines of ≥30% at 12 weeks and at any time on study thereafter | at week 12 | 
| rPFS | From date of start of treatment until the date of first documented progression or date of death from any cause, whichever came first | From date of start of treatment up to 6 months | 
| Disease control rate | Disease control rate at 12 and 24 weeks (defined as SD, PR, CR, see response criteria) | at 12 and 24 weeks |