Bladder Cancer
Conditions
Keywords
urothelial, bladder cancer, olaparib, durvalumab
Brief summary
The standard of care for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is rarely curative. Platinum-based neoadjuvant chemotherapy is associated with an improvement in Overall Survival (OS), but only a few patients can benefit from this approach. Therefore, new neoadjuvant treatments are required for muscle- invasive bladder cancer. In this study it will be explored the activity of durvalumab plus olaparib in advanced Transitional Cell Carcinoma of the Bladder and therefore may have beneficial outcomes in the neoadjuvant setting. Adverse events associated with durvalumab and olaparib is one of the potential risks in this study. Participation in this trial, in which 6-8 weeks of preoperative treatment will be administered, is not expected to result in delays of surgery for participants. It is not foreseen that treatment with durvalumab and olaparib has a relevant impact on operability or increases the risks associated with surgery
Interventions
DRUGDurvalumab
Infusion
DRUGOlaparib
P.O.
Sponsors
AstraZeneca
Sistemas Genómicos
Apices Soluciones S.L.
Spanish Oncology Genito-Urinary Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent obtained from the subject prior to performing any protocol related procedures, including screening evaluations 2. Age ≥18 years at time of study entry 3. Subjects with histological confirmation of T2-T4a urothelial bladder by transurethral resection 4. Patients aimed for cystectomy without neoadjuvant chemotherapy 5. Tumor tissue (archival or recent acquisition) from diagnostic Transurethral Resection (TUR) must be available (block or 5 - 15 unstained slides of formalin fixed paraffin embedded (FFPE) tissue) for correlative studies. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Exclusion criteria
. 7. Life expectancy of \> 16 weeks 8. Body weight \> 30kg 9. Normal organ and bone marrow function prior to administration of study treatment as defined below: * Haemoglobin \> 10.0 g/dL with no blood transfusion in the past 28 days * Absolute neutrophil count (ANC) 1.5 x (\> 1500 per mm3) * Platelet count ≥ 100 x 109/L (\>100,000 per mm3) * Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). * Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN * Serum creatinine Clearance \> 51 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance. 10. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects within 28 days of study treatment and confirmed prior to treatment on day 1. 11. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations. 12. Male patients and their partners, who are sexually active and of childbearing potential, must agree to the use of two highly effective forms of contraception in combination, throughout the period of taking study treatment and for 180 days after last dose of study drug(s) to prevent pregnancy in a partner. Female patients of child bearing potential and male patients with partners of child bearing potential, who are sexually active, must agree to the use of two highly effective forms of contraception throughout period of taking study treatment and for 1 month (female patients) / 3 months (male patients) after last dose of study drug. 13. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT/MRI and is suitable for repeated assessment. 14. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary cancer must be available for central testing. If there is not confirmation of the availability of an archived tumour sample prior to enrolment the patient is not eligible for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Impact of neoadjuvant treatment with durvalumab plus olaparib in the molecular profile of resectable urothelial bladder cancer (Pathological complete response rate (pCRR)) | 24 weeks | pCRR will be analysed based on the percentage of patients who obtained a pathological complete response. Pathologic response will be evaluated on cystectomy tumor sample |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Radiological response of durvalumab plus olaparib as presurgical treatment | 16 weeks | Radiological response will be assessed according to RECIST 1.1 criteria in patients with measurable and/or non-measurable disease at baseline that can be accurately assessed at baseline by computed tomography (CT) / magnetic resonance imaging (MRI) and is suitable for repeated assessment and previous to cystectomy. Patients without a radiologic post-baseline tumour assessment will be considered not evaluable for this endpoint. |
| Toxicity profile of durvalumab plus olaparib as presurgical treatment in bladder cancer | 28 weeks | Percentage of patients with each of the adverse event per grade |
Other
| Measure | Time frame | Description |
|---|---|---|
| Predictive and prognostic exploratory biomarkers in collected tumour tissue and plasma and their association with disease status and/or response/failure to study treatment | 24 weeks | Summary statistics and corresponding changes (or percent changes) from baseline tabulated by time and cohort |
Countries
Spain
Outcome results
None listed