Trimodality therapy with or without adjuvant Durvalumab to treat patients with bladder cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacion Cris De Investigacion Para Vencer El Cancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

6 Nov 2019 → ongoing

Decision date (initial)

2024-04-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca Inc. Canadá

External identifiers

EU CT number

2024-512502-26-00

EudraCT number

2019-001310-42

ClinicalTrials.gov

NCT03768570

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To determine whether durvalumab given after standard trimodality therapy improves disease-free survival when compared to surveillance alone in patients with T2 or more muscle-invasive bladder cancer

Secondary objectives 8

1. Compare non muscle-invasive bladder cancer recurrence rate (< T2)
2. Comparison of loco-regional control rate (LCR) between study arms at the 12 week visit
3. Compare overall and bladder intact disease-free survival between study arms
4. Compare patterns of disease recurrence between study arms
5. Compare metastasis-free survival between arms
6. Compare safety between study arms
7. Compare quality of life between study arms
8. Compare cost effectiveness and health economics between study arms

Conditions and MedDRA coding

Muscle-invasive bladder cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. 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
2. Stage T2-T4a N0M0 at time of diagnosis (AJCC-TNM version 8
3. CT scan of the chest/abdomen/pelvis within 8 weeks from enrollment, showing no evidence of metastatic disease
4. Patients must be ≥ 18 years of age
5. Patients must have a life expectancy greater than 6 months
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix I) and a body weight of > 30kg
7. Patients must have adequate hematologic reserve
8. Patients must have an estimated creatinine clearance ≥ 30 ml/min
9. Patients must have adequate liver function
10. All patients must have a tumour block from their primary tumour available and consent to release for correlative analyses
11. Patients have completed prior trimodality therapy (TMT) consisting of surgery, chemotherapy and radiation therapy treatment prior to enrollment on the BL.13 study Patients should begin protocol treatment within 42 days after completion of TMT
12. Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either english, french or spanish
13. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements
14. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre
15. In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient enrollment
16. Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 3 months following treatment. Women of childbearing potential will have a pregnancy test to determine eligibility as part of the Pre-Study Evaluation
17. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

Exclusion criteria 15

1. Pre-existing medical conditions precluding treatment
2. Pregnancy or lactating mothers
3. Received prior therapy with anti-PD-1, anti-PD-L1,anti-PD-L2, anti- CD137, anti-CTLA-4) antibody
4. 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
5. Patients with active or uncontrolled intercurrent illness including, but not limited to: • cardiac dysfunction • active peptic ulcer disease or gastritis • active bleeding diatheses • psychiatric illness • Tuberculosis • HIV virus infection.HIV– infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible; • known active hepatitis B infection • known active hepatitis C infection
6. History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction
7. Current or prior use of immunosuppressive medication within 28 days of study entry
8. Peripheral neuropathy ≥ grade 2
9. History of allergic or hypersensitivity reactions to any study drug or their excipients
10. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG or history of familial long QT syndrome
11. History of interstitial lung disease
12. Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy
13. Any condition that does not permit compliance with the protocol
14. Live attenuated vaccination administered within 30 days prior to randomization.
15. Any prior carboplatin based therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease-free survival. From randomization to either recurrent (local or distant) bladder cancer, a new primary bladder cancer or death from any cause

Secondary endpoints 1

1. Locoregional Control Rate (LCR) Bladder-intact Disease-Free Survival Overall Survival Evaluable for Adverse Events Evaluable for Quality of Life Assessment Evaluable for Economic Analysis

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacion Cris De Investigacion Para Vencer El Cancer

Sponsor organisation

Fundacion Cris De Investigacion Para Vencer El Cancer

Address

Avenida Manoteras 22, Poligono De Manoteras Poligono De Manoteras

City

Madrid

Postcode

28050

Country

Spain

Scientific contact point

Organisation

Fundacion Cris De Investigacion Para Vencer El Cancer

Contact name

Apices Soluciones - Clinical Operations department

Public contact point

Organisation

Fundacion Cris De Investigacion Para Vencer El Cancer

Contact name

Apices Soluciones - Clinical Operations department

Third parties 2

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

2 submissions — initial application plus substantial / non-substantial modifications