NCT03702179

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

Phase II Trial of Durvalumab (Medi4736) Plus Tremelimumab With Concurrent Radiotherapy in Patients With Localized Muscle Invasive Bladder Cancer Treated With a Selective Bladder Preservation Approach

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Spanish Oncology Genito-Urinary Group · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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. Six weeks after the end of radiotherapy, ALL patients will undergo a new cystoscopy with biopsies of the tumor bed and all residual present lesions as an efficacy determination. In patients with persistent prominent inflammatory reaction at this moment, the cystoscopy can be performed 1-2 weeks later (6 to 8 weeks after the end of radiotherapy). Response is defined as an absence of invasive cancer at post immunotherapy biopsy (≤cT1). Patients with response to immunotherapy will be candidates to bladder preservation, whereas in those with residual muscle invasive tumor the possibility of salvage radical cystectomy must be evaluated. Patients developing an isolated bladder invasive relapse during follow-up will be also possible candidates to salvage cystectomy, whereas those developing a superficial relapse in the preserved bladder will be managed with TUR and intravesical BCG. Patients will be followed up every 3 months the first year, every 4 months the second year and every 6 months thereafter with abdomen and pelvis CT scan, Rx thorax, urine cytology. Additionally, the mandatory efficacy cystoscopy and bladder biopsy (6w post RT), other cystoscopy and bladder biopsy will be performed in case of detection abnormalities in the cytology or imaging studies. The study will be closed 2 years after the last patient inclusion.

Conditions

• Invasive Bladder Cancer

Interventions

Type	Name	Description
DRUG	Durvalumab	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.
DRUG	Tremelimumab	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.
RADIATION	Radiotherapy	Radiotherapy at doses of 46 Gy to the minor pelvis and 64-66 Gy to the bladder.

Timeline

• Start date: 2018-11-19
• Primary completion: 2020-09-29
• Completion: 2022-08-16
• First posted: 2018-10-10
• Last updated: 2024-12-05
• Results posted: 2024-12-05

Locations

7 sites across 1 country: Spain