TRIO Bladder: A Study of Durvalumab Plus Tremelimumab Followed by Concurrent Durvalumab Plus Bladder Radiation in Muscle-Invasive Bladder Cancer

Withdrawn before enrolling · Phase 1

Conditions studied: Bladder Cancer

In brief

The purpose of this study is to describe the safety and tolerability of Durvalumab plus Tremelimumab followed by concurrent Durvalumab plus bladder radiation in patients with localized muscle invasive urothelial carcinoma of the bladder, who are either Decipher-Non-Basal OR Decipher-Basal and cisplatin-ineligible. Eligible subjects will receive 2 cycles of Durvalumab plus Tremelimumab followed by imaging and cystoscopy. Subjects whose cancer responds or is stable will receive a combination of 2 cycles of Durvalumab plus 6.5 weeks of radiation to the bladder followed by imaging and a TURBT. Subjects whose cancer continues to respond and meets certain criteria will continue to receive Durvalumab for up to 12 months from initial dose or until the cancer recoccurs or progresses, whichever occurs earlier. During this time, subjects may also receive intravesicular therapy if clinically indicated. Subjects will be followed for 5 years from initial dose.

Key facts

Study ID

NCT04073160

Run by

Daniel George, MD

People needed

0

Starts

2020-06-01

Expected to finish

2026-01-01

Last updated by the study team

2020-07-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Ability to understand and the willingness to sign a written informed consent document.
• Age ≥ 18 years
• Histologically or cytologically confirmed urothelial carcinoma of the bladder. Non-urothelial histologies and upper tract disease are excluded.
• Has clinical stage T2-T4b, N0-3, M0 urothelial carcinoma
• DECIPHER-Non-basal (Group A) OR DECIPHER-Basal but cisplatin-ineligible (Group B)
• a. Cisplatin-ineligible based on ≥1 of the following:
• i. CrCl <60 ml/min
• ii. Grade 2 hearing loss or peripheral neuropathy
• iii. ECOG performance status of 2
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy of at least 12 weeks
• Body weight >30kg
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥ 8.0 g/dL and asymptomatic
• Absolute neutrophil count (ANC ≥1.5 x 109/L)
• Platelet count ≥100 x 109/L
• Serum bilirubin ≤ 1.5 x Institutional Upper Limit of Normal (ULN) (Note: This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.)
• AST/SGOT and ALT/SGPT ≤ 2.5 x ULN
• Measured creatinine clearance (CL) >30 mL/min
• Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they meet the requirements below.
• Women < 45 years of age would be considered post-menopausal if they underwent surgical sterilization (bilateral oophorectomy or hysterectomy.
• Women 45 to <50 years of age would be considered post-menopausal if they have been amenorrheic for 18 months or more following cessation of exogenous hormonal treatments, if they have a documented follicle-stimulating hormone levels in the post-menopausal range (> 40 mlU/mL) or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
• Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, if they have a documented follicle-stimulating hormone levels in the post-menopausal range (> 40 mlU/mL) or underwent surgical sterilization (bilateral oophorecomy, bilateral salpingectomy or hysterectomy).
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

You may not qualify if…

• Subjects must not have any of the following:
• Prior systemic chemotherapy for bladder cancer
• Any prior treatment with CTLA-4, including tremelimumab PD-1 or PD-L1 including durvalumab checkpoint inhibitors
• Administration of an investigational therapeutic within 28 days prior to Cycle 1, Day 1
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤28 days prior to the first dose of study drug.
• Prior pelvic radiation that precludes bladder radiation
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
• Prior cystectomy
• Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Duke Principal Investigator.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Duke Principal Investigator.
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• 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)
• 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:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 5 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, 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

Where it is running

• Duke University Medical Center — Durham, North Carolina, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.