Durvalumab Plus Tremelimumab With Concurrent Radiotherapy for Localized Muscle Invasive Bladder Cancer Treated With a Selective Bladder Preservation Approach

Conditions

• Invasive Bladder Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Durvalumab — DRUG
  All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
• Tremelimumab — DRUG
  All patients will receive durvalumab (MEDI4736) (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) for up to 3 doses/cycles each, unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. If a patient's weight falls to 30kg or below the patient should receive weight-based dosing equivalent to 20 mg/kg of durvalumab Q4W and 1mg/kg tremelimumab Q4W until the weight improves to \>30 kg, at which point the patient should start receiving the fixed dosing of durvalumab 1500mg plus tremelimumab 75 mg Q4W.
• Radiotherapy — RADIATION
  Radiotherapy at doses of 46 Gy to the minor pelvis and 64-66 Gy to the bladder.

Study Details

Combined-modality treatment of localized muscle invasive bladder cancer including transurethral resection (TUR), radiotherapy and dual checkpoint inhibition immunotherapy could achieve pathological complete response in some patients. These patients could avoid to undergone radical surgery with radical cystectomy and preserve their bladder, without the side-effects associated with chemotherapy and surgery. This study has been design to determine the efficacy of durvalumab plus tremelimumab with concurrent radiotherapy in terms of pathological response rate in patients with localized muscle invasive bladder cancer treated with bladder preservation intent.

Key Dates

Start date

Nov 19, 2018

Status verified

Aug 2023

Primary completion

Sep 29, 2020

Completion

Aug 16, 2022

Study Design

Enrollment

32 participants (actual)

Allocation

NA

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Durvalumab + Tremelimumab
  The treatment consisted of initial TUR of the tumor, with multiple random biopsies of normal-appearing bladder urothelium, followed by durvalumab 1500 mg i.v. plus tremelimumab 75 mg i.v., every 4 weeks for a total of 3 doses. Two weeks after the initiation of immunotherapy, normofractionated external-beam radiotherapy with high-energy photons will be started. Radiotherapy will be administered concurrently with immunotherapy at doses of 46 Gy to the minor pelvis and 64-66 Gy to the bladder.

Primary Outcome Measure

Proportion of Patients With Pathological Response [ Time Frame: 12 weeks ]