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

NCT04073160 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: Pro00102352
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Bladder Cancer

Keywords

Muscle-invasive bladder cancer; Decipher bladder test; Durvalumab; Tremelimumab; Bladder radiation; Urothelial carcinoma of the bladder

Outcome Measures

Primary Outcomes (5)

• Incidence of adverse events

  To describe the safety and tolerability of durvalumab plus tremelimumab followed by concurrent durvalumab plus bladder radiation in patients as assessed by CTCAE version 5.0.

  Up to 90 days after the last dose of study drug(s)

• Incidence of serious adverse events

  To describe the safety and tolerability of durvalumab plus tremelimumab followed by concurrent durvalumab plus bladder radiation in patients as assessed by CTCAE version 5.0.

  Up to 90 days after the last dose of study drug(s)

• Incidence of adverse events of special interest

  To describe the safety and tolerability of durvalumab plus tremelimumab followed by concurrent durvalumab plus bladder radiation in patients as assessed by CTCAE version 5.0.

  Up to 90 days after the last dose of study drug(s)

• Incidence of adverse events leading to study drug discontinuation

  To describe the safety and tolerability of durvalumab plus tremelimumab followed by concurrent durvalumab plus bladder radiation in patients as assessed by CTCAE version 5.0.

  Up to 90 days after the last dose of study drug(s)

• Incidence of deaths

  To describe the safety and tolerability of durvalumab plus tremelimumab followed by concurrent durvalumab plus bladder radiation in patients as assessed by CTCAE version 5.0.

  Up to 90 days after the last dose of study drug(s)

Secondary Outcomes (5)

• 2-year disease-free survival (DFS) for Decipher test sub-type basal vs. Decipher test sub-type non-basal

  2 years

• Pathologic complete response rate on post-duravalumab/radiation TURBT

  Cycle 4 Day 21

• Rate of salvage cystectomy

  5 years

• 5-year disease-free survival (DFS)

  5 years

• 5-year overall survival (OS)

  5 years

Study Arms (2)

Decipher Bladder test subtype non-basal

EXPERIMENTAL

Subjects with localized muscle invasive urothelial carcinoma of the bladder, whose tumor is Decipher Bladder test subtype non-basal

Drug: Tremelimumab; Drug: Durvalumab; Radiation: Bladder radiation; Drug: Intravesicular Therapy

Decipher Bladder test subtype basal and cisplatin-ineligible

EXPERIMENTAL

Subjects with localized muscle invasive urothelial carcinoma of the bladder, whose tumor is Decipher Bladder test subtype basal and the subject is cisplatin-ineligible

Drug: Tremelimumab; Drug: Durvalumab; Radiation: Bladder radiation; Drug: Intravesicular Therapy

Interventions

Tremelimumab DRUG

Tremelimumab and durvalumab will be administered in combination during cycles 1 and 2. Tremelimumab will be administered intravenously at a dose of 75 mg on cycle 1 day 1 and cycle 2 day 1. Cycles are 4 weeks long.

Decipher Bladder test subtype basal and cisplatin-ineligible; Decipher Bladder test subtype non-basal

Durvalumab DRUG

Tremelimumab and durvalumab will be administered in combination during cycles 1 and 2. Durvalumab will be administered intravenously at a dose of 1500 mg on cycle 1 day 1 and cycle 2 day 1. Cycles are 4 weeks long. Eligible subjects may go on to receive a combination of durvalumab and bladder radiation during cycles 3 and 4. Durvalumab will be administered intravenously at a dose of 1500 mg on cycle 3 day 1 and cycle 4 day 1. At the completion of radiation, eligible subjects may continue to receive durvalumab for a maximum of one year from the date of their initial dose. Durvalumab will be administered intravenously at a dose of 1500 mg on the first day of each cycle.

Also known as: Imfinzi

Decipher Bladder test subtype basal and cisplatin-ineligible; Decipher Bladder test subtype non-basal

Bladder radiation RADIATION

During the durvalumab cycles 3 and 4, eligible subjects will receive 6.5 weeks of radiation to the bladder. Radiation will be administered at a dose of 64 Gy in daily 2 Gy fractions.

Decipher Bladder test subtype basal and cisplatin-ineligible; Decipher Bladder test subtype non-basal

Intravesicular Therapy DRUG

Subjects will receive intravesicular therapy, if clinically indicated during cycles 5 and beyond of durvalumab administration. Intravesicular therapy will consist of BCG, gemcitabine, mitomycin or a similar drug, depending on institutional standards and treating provider's discretion.

Decipher Bladder test subtype basal and cisplatin-ineligible; Decipher Bladder test subtype non-basal

Eligibility Criteria

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

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)

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
• 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)

Sponsors & Collaborators

• Daniel George, MD: lead
• AstraZeneca: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

tremelimumab; 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

• Tian Zhang, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 27, 2019
• First Posted: August 29, 2019
• Study Start: June 1, 2020
• Primary Completion: July 1, 2021
• Study Completion: January 1, 2026
• Last Updated: July 7, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)