Trimodality Therapy With/Out Durvalumab to Treat Patients With Muscle-Invasive Bladder Cancer

NCT03768570 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: BL132019-001310-42
• Study Type: interventional
• Target: 82
• Locations: 3 countries
• Sites: 31

Brief Summary

The purpose of this study is to find out what effects durvalumab has on bladder cancer, combined with treatment after completion of surgery, chemotherapy and radiotherapy.

Conditions

Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free survival

  defined as the time from the randomization to the time of the first event that is either recurrent (local or distant) bladder cancer, a new primary bladder cancer or death from any cause

  5 years

Secondary Outcomes (9)

• Non-muscle invasive bladder cancer recurrence rate

  5 years

• Loco-regional control rate between study arms at the 12 week visit

  5 years

• Patterns of disease recurrence between study arms

  5 years

• Compare overall and bladder intact disease-free survival between study arms

  5 years

• Metastasis-free survival between study arms

  5 years

Study Arms (2)

Surveillance

NO INTERVENTION

Durvalumab

ACTIVE COMPARATOR

Drug: Durvalumab

Interventions

Durvalumab DRUG

1500 mg IV on day 1 of 4 week cycle every 4 weeks for 12 months

Durvalumab

Eligibility Criteria

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

You may qualify if:

• Histologic diagnosis of urothelial carcinoma of the bladder. Patients with mixed histology (including small cell) and urothelial carcinoma are eligible. Patients with pure small cell carcinoma will be excluded.
• Stage T2-T4a N0M0 at time of diagnosis based on trans-urethral resection of bladder tumour, imaging, and/or bimanual examination under anesthesia.
• CT scan of the chest/abdomen/pelvis within 8 weeks from enrollment, showing no evidence of metastatic disease.
• Patients must be ≥ 18 years of age.
• Patients must have a life expectancy greater than 6 months.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and a body weight of \> 30kg.
• Patients must have adequate hematologic reserve: Platelet count ≥ 75 x 10\^9/L, Absolute neutrophils ≥ 1.0 x 10\^9/L. Anemia will be corrected to minimum hemoglobin of 90 g/L with red cell transfusions, if necessary.
• Patients must have an estimated creatinine clearance (Cockcroft-Gault Equation) ≥ 30 ml/min.
• Patients must have adequate liver function with a bilirubin ≤ 1.5 ULN (if confirmed Gilbert's, eligible providing bilirubin ≤ 3 x UNL) and AST/ALT (SGOT/SGPT) \< 2.5 x the upper normal limit.
• All patients must have a tumour block from their primary tumour available and consent to release the block/cores/cut slides for correlative analyses ( and the centre/pathologist must have agreed to the submission of the specimen(s).
• Patients have completed prior trimodality therapy (TMT) consisting of surgery, chemotherapy and radiation therapy treatment prior to enrollment. Patient should start treatment within 42 days after completion of TMT.
• Patients must have undergone a transurethral resection prior to study enrollment.
• Patient may have completed up to 4 cycles of cisplatin-based neo-adjuvant chemotherapy. Adjuvant chemotherapy is not permitted. Patients will have received cisplatin, given intravenously during the radiation therapy. OR Patients may have received fluorouracil and mitomycin given intravenously once weekly or gemcitabine as an alternative to cisplatin during radiotherapy.
• The following are radiotherapy guidelines for patients treated on study. Patients will be treated to radical treatment doses using IMRT, VMAT or 4 field conformal techniques. Planning will be based on CT planning. IGRT is recommended during the radiotherapy treatment. Recognizing differences in usual radiotherapy doses used in the various participating countries and centres the following would be acceptable doses in this study. The bladder CTV will include the whole empty bladder and any extravesical extension. PTV expansion will be a minimum of 0.75 cm right, left and inferiorly, 1.5 cm Anteriorly and superiorly and 1 cm posteriorly. These minimum expansions are with Cone beam verification. For patients undergoing RT without image-guided verification 1.5 cm expansion in all directions is recommended. Acceptable doses for this study include:
• Bladder only: 64-66 Gy in 32-33 fractions over 6.5 weeks; 50-55 Gy in 20 fractions over 4 weeks

You may not qualify if:

• Pre-existing medical conditions precluding treatment.
• Pregnancy or lactating mothers.
• Received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD-L1, including durvalumab anti-programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumour Necrosis Factor Receptor \[TNFR\] family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease: not due to radiation reaction), diverticulitis with the exception of diverticulosis, celiac disease (controlled by diet alone) or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Patients with alopecia;
• Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years);
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement;
• Any chronic skin condition that does not require systemic therapy.
• Patients with active or uncontrolled intercurrent illness including, but not limited to:
• cardiac dysfunction (symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia);
• active peptic ulcer disease or gastritis;
• active bleeding diatheses;
• psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent;
• known history of previous clinical diagnosis of tuberculosis;
• known active human immunodeficiency virus infection (positive HIV 1/2 antibodies). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible;

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator

Study Sites (31)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Thunder Bay Regional Health Sciences Centre/

Thunder Bay, Ontario, P7B 6V4, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

The Research Institute of the McGill University

Montreal, Quebec, H4A 3J1, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Hospital Clinic i Provincial

Barcelona, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Madrid Norte Sanchinarro

Madrid, 28050, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, 39008, Spain

Location

Instituto Valenciano de Oncologia

Valencia, 46009, Spain

Location

Royal Devon and Exeter Hospital

Exeter, Devon, EX2 5DW, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust

Cornwall, England, TR1 3LQ, United Kingdom

Location

Royal Preston Hospital

Lancashire, England, PR2 9HT, United Kingdom

Location

Charing Cross Hospital

London, England, VV6 8RF, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, United Kingdom

Location

The Royal Marsden NHS Foundation Trust - Sutton

Surrey, England, United Kingdom

Location

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, SO16 6YD, United Kingdom

Location

Nottingham University Hospitals City Hospital Campus

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

durvalumab

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

• Wassim Kassouf

  The Research Institute of the McGill University, Montreal QC Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2018
• First Posted: December 7, 2018
• Study Start: October 25, 2019
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 2, 2026

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (15); GB (8); ES (8)