Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer

Description

STUDY DESIGN:

Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder.

The bladder preserving therapy include combined modality therapy with:

STUDY TREATMENTS:

Investigational product (atezolizumab/Tecentriq ):

• Route of administration: intravenous infusion.
• Duration of treatment: 16 weeks.
• Dosage: 1.200 mg intravenous every 3 weeks for a total of 6 doses. Atezolizumab is supplied as atezolizumab 1200 mg/20 mL vials (60 mg/mL) solution for intravenous infusion. After dilution, one mL of solution should contain approximately 4.4 mg of atezolizumab (1,200 mg/270 mL).

External Beam Radiation Therapy (EBRT): radiation

• Duration of treatment: 6 weeks
• Dosage: 60 Gy of radiotherapy in 30 fractions overs 6 weeks at 2Gy/day

STUDY POPULATION:

Adult patients (aged 18 years) with histologically confirmed diagnosis of muscle-invasive urothelial carcinoma of the bladder, in clinical stages T2-T4a who are not candidates for radical cystectomy by medical reasons, refusal or patients choice.

A total of 39 patients are estimated to be included in the study.

OBJECTIVES

Primary objective:

The primary objective of the study is to determine the efficacy of atezolizumab concurrent with radiotherapy in terms of pathological complete response defined as a response of grade 5 according to Miller and Payne criteria in patients with muscle-invasive bladder cancer treated with bladder preservation intent.

Secondary objectives:

• To evaluate overall survival (OS).
• To evaluate disease specific survival (DSS).
• To evaluate disease free survival (DFS).
• To evaluate bladder intact disease-free survival (BIDFS).
• To calculate the number of patients with muscle invasive and non-muscle invasive local failure (LF).
• To determine the rate of distance metastases defined as the percentage of patients who develop metastases.
• To determine to the rate of patients with bladder preserved.
• To determine to the rate of immediate or late salvage cystectomy.
• The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy.

Exploratory objectives:

• To determine the predictive role of the expression of PD-1 / PD-L1 and CD8 in terms of pCR, OS and DFS in bladder cancer patients treated with atezolizumab plus radiotherapy.
• The correlation between the levels of IFN-, interleukin 6 (IL-6), interleukin 18 (IL-18), or ITAC (also called CXCL11 or IP-9) and the efficacy parameters (pCR, OS and DFS) of the treatment with atezolizumab plus radiotherapy.

STUDY VISITS AND PROCEDURES:

The study includes the following visits:

• Screening: within the 28 days prior to starting the study treatment.
• Baseline visit: the first day of cycle 1
• Visits over the treatment period (16 weeks 7 days): from administration of the first dose of the study treatment to the administration of the last dose of atezolizumab or withdrawal from the treatment. Treatment will consist of the administration of atezolizumab at 1,200 mg intravenous every 3 weeks for 6 cycles
• Post-treatment follow-up: includes the biopsy and safety visit 1-2 months after the last dose of atezolizumab and a subsequent 5 years follow-up period after.
• End of study visit/ Early termination: In patients who end the study follow-up or prematurely withdraw from the study

Details