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

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

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

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Other: chemoradiotherapy; Biological: Nivolumab

Detailed 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

• Study Type: Interventional
• Enrollment (Anticipated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Vasiliki Magoula, MSc; Phone Number: +302107777791; Email: res2@eeoogek.gr

Study Locations

• Greece
  • Attica
    • Athens, Attica, Greece, 11527
      • Recruiting
      • Hellenic GenitoUrinary Cancer Group
      • Contact: Aristotelis Bamias, Professor; Phone Number: 00302107777791; Email: abamias@med.uoa.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chemoradiotherapy; standard of care chemo-radiotherapy	Other: chemoradiotherapy; standard of care chemoradiotherapy
Experimental: Combination; standard of care chemo-radiotherapy + Nivolumab	Other: chemoradiotherapy; standard of care chemoradiotherapy; Biological: Nivolumab; standard of care chemoradiotherapy + Nivolumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Hellenic GenitoUrinary Cancer Group

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: June 4, 2019
• First Submitted That Met QC Criteria: June 18, 2019
• First Posted (Actual): June 20, 2019

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: REQ-0000020479

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No