Nivolumab Plus Chemoradiotherapy in Patients With Muscle-invasive Bladder Cancer (MIBC) Not Undergoing Cystectomy

Bladder Cancer Clinical Trial

Official title:

Nivolumab Plus Chemoradiotherapy in Patients With Muscle-invasive Bladder Cancer (MIBC) Not Undergoing Cystectomy: a Phase II, Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03993249
• Other study ID #: REQ-0000020479
• Status: Recruiting
• Phase: Phase 2
• Start date: May 28, 2019
• Est. completion date: December 2023

Study information

• Verified date: March 2022
• Source: Hellenic GenitoUrinary Cancer Group
• Contact: Vasiliki Magoula, MSc
• Phone: +302107777791
• Email: res2[@]eeoogek.gr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to investigate the effect synchronous use of nivolumab in addition to chemoradiotherapy in patients withnon-metastatic MIBC who are not candidates for radical cystectomy

Description:

The initial hypothesis is that addition of nivolumab will increase 2-year locoregional control rate from 55% (control arm) to 75% (immunotherapy arm)

There is a 24 month accrual period during which 78 patients will be randomized in a control group (standard chemo-radiotherapy) and the treatment group (chemo-radiotherapy + Nivolumab)

The primary objective would be to compare locoregional control rate at 2-years between patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy.

The secondary objectives are

1. To study the safety of the addition of nivolumab to chemoradiotherapy in patients with MIBC

2. To compare 2-year bladder cancer failure-free (BCFF) rates, defined as distant metastasis free survival (MFS) AND/OR locoregional failure (defined as in primary objective)

3. To compare median overall survival (OS) in patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy

4. Assess the effect of combined treatment on the quality of life

Correlative studies of outcomes with PD-L1expression and with lymphocytic populations in the environment of the tumor

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 2023
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically proven, muscle-invasive carcinoma of the bladder, cT2-T4aN0M0

• Urothelial, squamous or glandular histology according to WHO 2016 classification (Fig 1)

• Undergone a vigorous TURB

• Not candidates for radical cystectomy.

• PS:0-1

• age >18 years old

• Adequate bone marrow function

• Adequate renal function

Exclusion Criteria:

Key Exclusion Criteria

• Histology other than transitional-cell, squamous or adenocarcinoma

• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, prostate cancer cervix or breast.

• Previous systemic chemotherapy or prior biologic agents within 4 weeks, or intravesical Bacillus Calmette-Guerin (BCG) within 6 weeks of the first dose of study treatment.

• Prior treatment with any PD-1 or PDL-1 inhibitor or anti CTLA4 agent

• Previous pelvic radiation therapy.

• Patients with inherited syndromes associated with hypersensitivity to ionizing radiation

• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation

• Any history of inflammatory bowel disease and or history of abdominal fistula

• Previous allergy to any of the study drugs

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Biological:
• Nivolumab
standard of care chemoradiotherapy + Nivolumab

Other:
• chemoradiotherapy
standard of care chemoradiotherapy

Locations

Country	Name	City	State
Greece	Hellenic GenitoUrinary Cancer Group	Athens	Attica

Sponsors (1)

Lead Sponsor	Collaborator
Hellenic GenitoUrinary Cancer Group

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Locoregional control rate	To compare locoregional control rate at 2-years between patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy	2 years
Secondary	Incidence Rate of treatment-related adverse event (safety and tolerability)	Incidence of adverse events as assessed by CTCAE. After radiotherapy completion, AEs will be assessed according to RTOG/EORTC Late Radiation Morbidity Scoring Schema	2 years
Secondary	Bladder cancer failure-free (BCFF) rates	To compare 2-year bladder cancer failure-free (BCFF) rates, defined as distant metastasis free survival (MFS) AND/OR locoregional failure (defined as in primary objective)	2 years
Secondary	Median overall survival (OS)	To compare median overall survival (OS) in patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy	2 years
Secondary	Assessment of the effect of the combined treatment on the quality of life	Quality of life score assessed by Quality of Life of Cancer Patients Questionnaire (EORTC QLQ-C30). Discomfort measured in a scale from 1 (not at all) to 4 (very much) Overall health and quality of life score measured in a scale from 1 (very poor) to 7 (excellent)	2 years