Carboplatin in Castration-resistant Prostate Cancer

Study Overview
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Brief Summary
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Open label, non-randomised phase II clinical pilot study

Detailed Description
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Pilot Study of weekly Carboplatin in Patients with Advanced Metastatic Castration-Resistant Prostate Cancer (CRPC) and DNA repair defects

Official Title
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Single Arm Open Label Phase II Pilot Study of Carboplatin in Patients With Metastatic Castrationresistant Prostate Cancer (CRPC) and PTEN Loss and/or DNA Repair Defects

Conditions
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Prostatic Neoplasm

Intervention / Treatment
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* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written Informed Consent Adult patients with histological diagnosis of adenocarcinoma of the prostate. Metastatic Castration-Resistant Prostate Cancer (mCRPC) Progression after at least one taxane-based chemotherapy (or contraindication against taxanes) and at least one therapy with a newer hormonal agent (Cyp17 inhibitor or a new generation AA like enzalutamide). DNA repair defects as per central assessment Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0 - 2 Progression of disease by any of the criteria listed here: PSA utilizing PCWG 2 criteria Bone scan RECIST 1.1 Adequate organ and bone marrow function as evidenced by: Haemoglobin ≥8.0 g/dL Absolute neutrophil count ≥1.5 x 109/L Platelet count ≥ 100 x 109/L AST and/or ALT < 2.5 x ULN, in the presence of liver metastases: AST ≥5 x ULN, ALT <5 x ULN Total bilirubin < 2.0 x ULN (except for patients with Gilbert's disease) Creatinine Clearance ≥30ml/min Patient must agree in the biomarker studies including the fresh tumour biopsies Exclusion Criteria: Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product Carboplatin Prior treatment with any prior platinum based chemotherapy, Major surgery within 4 weeks prior to planned start of treatment Known brain or leptomeningeal involvement unless clinically stable and on stable dose of steroids Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant Previous enrolment into the current study Active secondary malignancy that requires systemic therapy.

Ages Eligible for Study
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Minimum Age: 18 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: Carboplatin<br>Carboplatin will be administered weekly | Drug: Carboplatin<br>* Carboplatin will be administered weekly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response | Soft tissue or PSA Response | Time Frame: Up to the end of the treatment phase (ie, approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of PSA declines of ≥30% | PSA | Time Frame: At 12 weeks and up to the end of the treatment phase (ie, approximately 6 months) | 
| OS | Overall survival (OS) form start of Carboplatin | Time Frame: livelong follow-up | 
| rPFS | Radiological progression-free survival (rPFS) from start of carboplatin | Time Frame: Up to the end of the treatment phase (ie, approximately 6 months | 
| PSA | Time to PSA progression | on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | 
| Safety as per CTC AEv4.03 | Number of patients with adverse events | on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | 
| Disease control rate | Disease control rate at 12 and 24 weeks (defined as SD, PR, CR, see response criteria | On studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | 
| PTEN loss | Evaluation of PTEN loss by FISH (Frequency and correlation with IHC) | Pre-study biopsy sample |