Durvalumab Plus Olaparib Administered Prior to Surgery of Resectable Urothelial Bladder Cancer (NEODURVARIB)

NCT03534492 | Completed Phase 2

• 2 other identifiers: SOGUG-2017-A-IEC(VEJ)-22017-002765-22
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 10

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

Conditions

Bladder Cancer

Keywords

urothelial; bladder cancer; olaparib; durvalumab

Outcome Measures

Primary Outcomes (1)

• Impact of neoadjuvant treatment with durvalumab plus olaparib in the molecular profile of resectable urothelial bladder cancer (Pathological complete response rate (pCRR))

  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

  24 weeks

Secondary Outcomes (2)

• Radiological response of durvalumab plus olaparib as presurgical treatment

  16 weeks

• Toxicity profile of durvalumab plus olaparib as presurgical treatment in bladder cancer

  28 weeks

Other Outcomes (1)

• 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

Study Arms (1)

Durvalumab plus Olaparib

EXPERIMENTAL

Durvalumab 1500 mg every 4 weeks for up to a maximum of 2 months (up to 2 doses/cycles) plus Olaparib 300 mg b.i.d. up to 56 days (2 cycles of 28 days each cycle).

Drug: Durvalumab; Drug: Olaparib

Interventions

Durvalumab DRUG

Infusion

Durvalumab plus Olaparib

Olaparib DRUG

P.O.

Durvalumab plus Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the subject prior to performing any protocol related procedures, including screening evaluations
• Age ≥18 years at time of study entry
• Subjects with histological confirmation of T2-T4a urothelial bladder by transurethral resection
• Patients aimed for cystectomy without neoadjuvant chemotherapy
• 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.

You may not qualify if:

• Life expectancy of \> 16 weeks
• Body weight \> 30kg
• 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.
• 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.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
• 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.
• 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.
• 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
• Participation in another clinical study with an investigational product during the last 4 weeks

Sponsors & Collaborators

• Spanish Oncology Genito-Urinary Group: lead
• AstraZeneca: collaborator
• Sistemas Genómicos: collaborator
• Apices Soluciones S.L.: collaborator

Study Sites (10)

ICO Badalona

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Clinica IMQ Zorrotzaurre

Bilbao, Spain

Location

Hospital San Pedro de Alcántara

Cáceres, Spain

Location

Hospital Universitario Lucus Augusti

Lugo, 27003, Spain

Location

Hospital Ramón Y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hopsital Universitario Madrid Sanchinarro (CIOCC)

Madrid, Spain

Location

Hospital de Navarra

Pamplona, Spain

Location

Hospital Virgen Macarena

Seville, Spain

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

durvalumab; olaparib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Jesús García-Donas, MD PhD

  Centro Integral Oncológico Clara Campal

  PRINCIPAL INVESTIGATOR

• Juan F Rodriguez-Moreno, MD

  Centro Integral Oncológico Clara Campal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2018
• First Posted: May 23, 2018
• Study Start: November 16, 2018
• Primary Completion: March 16, 2020
• Study Completion: March 16, 2020
• Last Updated: April 6, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (10)