Efficacy of Atezolizumab Concurrent With Radiotherapy in Patients With Muscle-invasive Bladder cáncer
- Conditions
- Bladder Cancer
- Interventions
- Radiation: External Beam Radiation Therapy (EBRT)
- Registration Number
- NCT04186013
- Lead Sponsor
- Spanish Oncology Genito-Urinary Group
- Brief Summary
Open, multicentre, phase II trial of atezolizumab with concurrent normofractionated radiotherapy in patients with localized muscle-invasive bladder cancer treated with a selective multimodality bladder conservative approach.
- Detailed 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 patient´s 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-γ, 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 39
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental arm Atezolizumab Injection [Tecentriq] Atezolizumab 1200 mg intravenous infusion every 3 weeks for a total of 6 doses combined with External Beam Radiation Therapy (EBRT) (dosage: 60 Gy in 30 fractions overs 6 weeks at 2Gy/day) Experimental arm External Beam Radiation Therapy (EBRT) Atezolizumab 1200 mg intravenous infusion every 3 weeks for a total of 6 doses combined with External Beam Radiation Therapy (EBRT) (dosage: 60 Gy in 30 fractions overs 6 weeks at 2Gy/day)
- Primary Outcome Measures
Name Time Method Pathological complete response After the end of the treatment (16 weeks) Response of grade 5 according to Miller and Payne criteria
- Secondary Outcome Measures
Name Time Method Disease specific survival through study completion, up to 5 years Time from start of treatment to the date of having evidence of distant metastases, nodal recurrence or recurrence within the radiotherapy field that could be salvaged in a curative fashion, what happens first
Muscle invasive and non-muscle invasive local failure through study completion, up to 5 years defined as patients that do not achieve a pCR defined as a response of grade 5 according to Miller and Payne criteria and documented tumour recurrence after pCR
Overall survival through study completion, up to 5 years Time from the date of the beginning of protocol therapy to the date of death due to any cause
Disease free survival through study completion, up to 5 years Time from the date of start of protocol therapy to the date of recurrence of muscle invasive or non-invasive bladder carcinoma or metastases, what happens first
Bladder-intact disease-free survival through study completion, up to 5 years Time from the date of initiation of protocol therapy until the development of MIBC recurrence, regional pelvic recurrence, distant metastases, bladder cancer-related death or cystectomy, what happens first
Rate of patients with bladder preserved through study completion, up to 5 years Rate of patients with bladder preserved at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab
Rate of distant metastases through study completion, up to 5 years Percentage of patients who develop distant metastases. Defined as lymphonodal involvement above the bifurcation of the iliac vessels or in inquinal regions and metastases resulting from hematogenous spread
Rate of immediate or late salvage cystectomy through study completion, up to 5 years Immediate will be evaluated at the time of the biopsy of the tumour performed between one and two months after the last dose of atezolizumab and late will be evaluated during the follow-up
The safety profile and tolerability of the combination of atezolizumab with concurrent radiotherapy through study completion, up to 5 years Collection of any adverse events and serious adverse events
Trial Locations
- Locations (10)
Consorci Corporació Sanitària Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital Clínico Universitario San Cecilio
🇪🇸Granada, Spain
Hospital Universitario Lucus Augusti
🇪🇸Lugo, Spain
Hospital HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario La Princesa
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario Ourense
🇪🇸Orense, Spain
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Spain
Hospital Arnau de Vilanova
🇪🇸Valencia, Spain
Hospital Universitario Sant Joan de Reus
🇪🇸Reus, Tarragona, Spain
Althaia Xarxa Assintencial
🇪🇸Manresa, Barcelona, Spain