Prostatic Neoplasm
Conditions
Brief summary
Open label, non-randomised phase II clinical pilot study
Detailed description
Pilot Study of weekly Carboplatin in Patients with Advanced Metastatic Castration-Resistant Prostate Cancer (CRPC) and DNA repair defects
Interventions
DRUGCarboplatin
Carboplatin will be administered weekly
Sponsors
Teva Pharma
University Hospital, Zürich
Aurelius Omlin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | Time Frame: Up to the end of the treatment phase (ie, approximately 6 months | Soft tissue or PSA Response |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS | Time Frame: livelong follow-up | Overall survival (OS) form start of Carboplatin |
| rPFS | Time Frame: Up to the end of the treatment phase (ie, approximately 6 months | Radiological progression-free survival (rPFS) from start of carboplatin |
| PSA | on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | Time to PSA progression |
| Rate of PSA declines of ≥30% | Time Frame: At 12 weeks and up to the end of the treatment phase (ie, approximately 6 months) | PSA |
| Disease control rate | On studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | Disease control rate at 12 and 24 weeks (defined as SD, PR, CR, see response criteria |
| PTEN loss | Pre-study biopsy sample | Evaluation of PTEN loss by FISH (Frequency and correlation with IHC) |
| Safety as per CTC AEv4.03 | on studyTime Frame: Up to the end of the treatment phase (ie, approximately 6 months | Number of patients with adverse events |
Countries
Switzerland
Outcome results
None listed