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

Primary Purpose

Bladder Cancer

Status
Recruiting
Phase
Phase 2
Locations
Greece
Study Type
Interventional
Intervention
Nivolumab
chemoradiotherapy
Sponsored by
Hellenic GenitoUrinary Cancer Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bladder Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hellenic GenitoUrinary Cancer GroupRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Chemoradiotherapy

Combination

Arm Description

standard of care chemo-radiotherapy

standard of care chemo-radiotherapy + Nivolumab

Outcomes

Primary Outcome Measures

Locoregional control rate
To compare locoregional control rate at 2-years between patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy

Secondary Outcome Measures

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

Full Information

First Posted
June 4, 2019
Last Updated
March 22, 2022
Sponsor
Hellenic GenitoUrinary Cancer Group
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1. Study Identification

Unique Protocol Identification Number
NCT03993249
Brief Title
Nivolumab Plus Chemoradiotherapy in Patients With Muscle-invasive Bladder Cancer (MIBC) Not Undergoing Cystectomy
Official Title
Nivolumab Plus Chemoradiotherapy in Patients With Muscle-invasive Bladder Cancer (MIBC) Not Undergoing Cystectomy: a Phase II, Randomized Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 28, 2019 (Actual)
Primary Completion Date
August 2022 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hellenic GenitoUrinary Cancer Group

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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
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 To study the safety of the addition of nivolumab to chemoradiotherapy in patients with MIBC 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) To compare median overall survival (OS) in patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized controlled
Masking
None (Open Label)
Allocation
Randomized
Enrollment
78 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Chemoradiotherapy
Arm Type
Other
Arm Description
standard of care chemo-radiotherapy
Arm Title
Combination
Arm Type
Experimental
Arm Description
standard of care chemo-radiotherapy + Nivolumab
Intervention Type
Biological
Intervention Name(s)
Nivolumab
Intervention Description
standard of care chemoradiotherapy + Nivolumab
Intervention Type
Other
Intervention Name(s)
chemoradiotherapy
Intervention Description
standard of care chemoradiotherapy
Primary Outcome Measure Information:
Title
Locoregional control rate
Description
To compare locoregional control rate at 2-years between patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Incidence Rate of treatment-related adverse event (safety and tolerability)
Description
Incidence of adverse events as assessed by CTCAE. After radiotherapy completion, AEs will be assessed according to RTOG/EORTC Late Radiation Morbidity Scoring Schema
Time Frame
2 years
Title
Bladder cancer failure-free (BCFF) rates
Description
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)
Time Frame
2 years
Title
Median overall survival (OS)
Description
To compare median overall survival (OS) in patients with MIBC receiving or not receiving nivolumab in addition to chemoradiotherapy
Time Frame
2 years
Title
Assessment of the effect of the combined treatment on the quality of life
Description
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)
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Vasiliki Magoula, MSc
Phone
+302107777791
Email
res2@eeoogek.gr
Facility Information:
Facility Name
Hellenic GenitoUrinary Cancer Group
City
Athens
State/Province
Attica
ZIP/Postal Code
11527
Country
Greece
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aristotelis Bamias, Professor
Phone
00302107777791
Email
abamias@med.uoa.gr

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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