Treatment combination of Durvalumab, Tremelimumab and Enfortumab Vedotin or Durvalumab and Enfortumab Vedotin in patients with muscle invasive bladder cancer ineligible to cisplatin or Who Refuse Cisplatin

JRCT ID: jRCT2031210667

Registered date:14/03/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Muscle Invasive Bladder Cancer
• Date of first enrollment: 22/07/2022
• Target sample size: 66
• Countries of recruitment: Argentina,Japan,Austria,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,Colombia,Japan,France,Japan,Germany,Japan,Greece,Japan,Hong Kong,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Mexico,Japan,Netherlands,Japan,Poland,Japan,Portugal,Japan,Russian Federation,Japan,Serbia,Japan,Spain,Japan,Taiwan,Japan,Thailand,Japan,Turkey,Japan,Ukraine,Japan,United Kingdom,Japan,United States,Japan,Vietnam,Japan
• Study type: Interventional

Intervention(s)

Arm 1:
- Neoadjuvant treatment for three 21-day cycles (ie, Neoadjuvant Weeks 1 through 9) with durvalumab 1500 mg (Day 1 of each cycle) + tremelimumab 75 mg (Cycle 1 Day 1 and Cycle 2 Day 8 only) + EV 1.25 mg/kg (Day 1 and Day 8 of each cycle)
- Radical cystectomy
- Adjuvant treatment for nine 28-day cycles (ie, Adjuvant Weeks 1 through 36) with durvalumab 1500 mg (Day 1 of each cycle) + tremelimumab 75 mg (Day 1 of first cycle only)
Arm 2:
- Neoadjuvant treatment for three 21-day cycles (ie, Neoadjuvant Weeks 1 through 9) with durvalumab 1500 mg (Day 1 of each cycle) + EV 1.25 mg/kg (Day 1 and Day 8 of each cycle)
- Radical cystectomy
- Adjuvant treatment for nine 28-day cycles (ie, Adjuvant Weeks 1 through 36) with durvalumab 1500 mg (Day 1 of each cycle)
Arm 3:
- No neoadjuvant treatment
- Radical cystectomy
- No adjuvant treatment; however, participants may receive adjuvant therapy if approved by local health authorities as a standard of care and available in the local market. Currently, only nivolumab is approved as adjuvant treatment for MIBC based on pathological high risk criteria (defined as pT3, pT4, or pN+).
Optional local standard platinum-based adjuvant treatment for Japanese patients with pT3/4 and/or pN+ disease after consultation with AstraZeneca (ie, gemcitabine with either cisplatin [eg, full-dose, low-dose, or split-dose] or carboplatin [AUC 4-5] for 2-4 cycles).

Outcome(s)

Primary Outcome

- Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on pCR rate
Pathologic complete response (pCR) rate is defined as the number of participants whose pathological staging was T0N0M0 as assessed per central pathological review using specimens obtained via cystectomy, up to 3 years.
- Compare efficacy of durvalumab + tremelimumab + EV relative to cystectomy alone on EFS
Event-free survival (EFS;) is defined as the time from randomization to the first occurrence of any of the following events: recurrence of disease post-radical cystectomy, the first documented progression in participants who did not receive radical cystectomy, failure to undergo radical cystectomy in participants with residual disease, or death due to any cause, up to 3 years.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Histologically or cytologically documented muscle-invasive UC of the bladder.
-Participants with transitional cell and mixed transitional/non-transitional cell histologies;
-Participants with MIBC clinical tumor (T) stage T2-T4aN0/1M0 or UC of the bladder with clinical state T1N1M0.
-Participants should also have not received prior systemic chemotherapy or immunotherapy for the treatment of MIBC or bladder UC.
- Medically fit for cystectomy and able to receive neoadjuvant therapy;
- Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC;
- ECOG performance status of 0,1,2 at enrollment.
- Availability of tumor sample prior to study entry.
- Must have a life expectancy of at least 12 weeks at randomization.
- Cisplatin-ineligible OR Refuse cisplatin based chemotherapy (must be documented in the medical records)

Exclude criteria

-Evidence of lymph node (N2+) or metastatic TCC/UC disease at the time of screening.
-Active infection
-Uncontrolled intercurrent illness
-Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti--PD-1, anti PD-L1, or anti-PD-L2
antibodies.
-Current or prior use of immunosuppressive medication within 14 days before the first dose of IPs.

Related Information

• Primary Sponsor: Boulous Suliman
• Secondary ID(s): NCT04960709