Trial of Local Cystoscopic Injection of Tremelimumab Plus Systemic Durvalumab for High Risk Non-Muscle Invasive Bladder Cancer

  • STATUS
    Recruiting
  • End date
    Sep 1, 2026
  • participants needed
    48
  • sponsor
    University of British Columbia
Updated on 25 November 2021
radical cystectomy
carcinoma
hormone therapy
carcinoma in situ
durvalumab
invasive bladder cancer
bladder tumor

Summary

We will conduct a Phase I trial testing whether local cystoscopic injection of tremelimumab into the bladder wall in combination with systemic administration of durvalumab in localized bladder cancer will stimulate an effective anti-tumour immune response with minimal systemic immune response and clinical toxicity.

Description

The Rideau trial is a multi-centre, prospective, randomized phase I/II trial to determine whether the local cystoscopic injection of tremelimumab into the bladder wall in combination with systemic administration of durvalumab in localized bladder cancer will stimulate an effective anti-tumour immune response with minimal systemic immune response and clinical toxicity. The study will be broken down into a dose escalation phase, to determine the recommended phase II dose of each drug in combination, and a dose expansion phase, to demonstrate an early signal of treatment efficacy (complete response at 6 months) in patients with BCG-unresponsive carcinoma in situ of the bladder. A maximum of 48 patients will be enrolled from 3 participating sites across Canada. All patients with histologically proven bladder cancer scheduled to undergo radical cystectomy at the trial hospital will be eligible for the dose escalation phase, while patients must have histologically proven, recurrent urothelial carcinoma in situ of the bladder to be eligible for the dose expansion phase. The dose escalation phase will run with between 12-36 patients who will receive 18 weeks of follow-up to determine the recommended phase II dose. Twelve patients will be enrolled in the dose expansion phase. These patients will receive follow-up every 4 weeks for 48 weeks, and then every 3 months for a total follow-up period of 24 months.

Details
Condition Urologic Cancer, Bladder Carcinoma, Bladder Cancer, bladder cancer, carcinoma of the bladder, urinary tract neoplasm, tremelimumab, High-Risk Cancer, Non-muscle Invasive, durvalumab, Bladder Disorders, bladder tumor, bladder disorder, Urothelial Cancer
Treatment tremelimumab
Clinical Study IdentifierNCT05120622
SponsorUniversity of British Columbia
Last Modified on25 November 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects with Grade 2 neuropathy will be evaluated on a case-by-case basis after consultation with the QI
Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the QI. 6. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. Subjects must not require treatment with a RANKL inhibitor (e.g. denosumab) who cannot discontinue it before treatment with durvalumab/tremelimumab. 7. Subjects must not have received any prior radiation to the bladder for bladder cancer. 8. Major surgical procedure (as defined by the QI) within 28 days prior to the first dose of IP. Note: Local surgery including bladder biopsy or transurethral bladder tumour resection is acceptable. 9. History of allogenic bone marrow or solid organ transplantation. 10. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion
Subjects with vitiligo or alopecia
Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
Any chronic skin condition that does not require systemic therapy
Subjects without active disease in the last 5 years may be included but only after consultation with the study physician
Subjects with celiac disease controlled by diet alone 11. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection (requiring oral or IV antibiotics within 14 days prior to registration), symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 12. History of another primary malignancy except for
Malignancy treated with curative intent and with no known active disease 5 years before the first dose of IP and of low potential risk for recurrence
Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
Adequately treated carcinoma in situ without evidence of disease
Low risk prostate cancer (according to National Comprehensive Cancer Network (NCCN) risk classification) on active surveillance 13. History of active primary immunodeficiency 14. Subjects positive for HIV are eligible only if they have all of the following
A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard PCR-based tests
A stable regimen of highly active anti-retroviral therapy (HAART)
No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections 15. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 16. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab. The following are exceptions to this criterion
Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Subjects, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. 18. Female subjects who are pregnant or breastfeeding or male or female subjects of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab + tremelimumab combination therapy. 19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 20. Prior randomisation or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment. 21. Judgment by the investigator that the patient is unsuitable to participate in the study and the patient is unlikely to comply with study procedures, restrictions and requirements. 22. Urethral stricture disease, other infravesical obstruction or other condition that will significantly impede cystoscopic injection of tremelimumab. This would include also oral anticoagulation other than 81 mg acetylsalicylic acid or non-steroidal anti-inflammatory drug (NSAID) if the patient is not able to interrupt anticoagulation or use low molecular weight heparin for bridging around the time of cystoscopic injection of tremelimumab
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