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

Phase 1

• Conditions: MedDRA version: 20.1 Level: PT Classification code 10066753 Term: Bladder transitional cell carcinoma stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Muscle-invasive bladder cancer; MedDRA version: 20.1 Level: PT Classification code 10066754 Term: Bladder transitional cell carcinoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-001310-42-ES
• Lead Sponsor: Canadian Cancer Trials Group (CCTG)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-09
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 238

Inclusion Criteria

1. Histologic diagnosis of urothelial carcinoma of the bladder
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
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 138

Exclusion Criteria

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, diverticulitis with the exception of diverticulosis, celiac disease, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener síndrome, 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
• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified