Carboplatin in Castration-resistant Prostate Cancer

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

Open label, non-randomised phase II clinical pilot study

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

Inclusion Criteria:

1. Written Informed Consent

2. Adult patients with histological diagnosis of adenocarcinoma of the prostate.

3. Metastatic Castration-Resistant Prostate Cancer (mCRPC)

4. 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).

5. DNA repair defects as per central assessment

6. Eastern Cooperative Oncology Group (ECOG) performance Status (PS) 0 - 2

7. Progression of disease by any of the criteria listed here:

   • PSA utilizing PCWG 2 criteria
   • Bone scan
   • RECIST 1.1

8. 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

9. Patient must agree in the biomarker studies including the fresh tumour biopsies

Exclusion Criteria:

1. Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product Carboplatin
2. Prior treatment with any prior platinum based chemotherapy,
3. Major surgery within 4 weeks prior to planned start of treatment
4. Known brain or leptomeningeal involvement unless clinically stable and on stable dose of steroids
5. Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
6. Previous enrolment into the current study
7. Active secondary malignancy that requires systemic therapy.