Various Advanced Cancer
Conditions
Brief summary
The purpose of this study is to determine the effectiveness and safety of Nivolumab compared to placebo in participants who have undergone radical surgery for invasive urothelial cancer.
Interventions
BIOLOGICALNivolumab
OTHERPlacebo
Sponsors
Bristol-Myers Squibb
Ono Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis * Must have had radical surgical resection (e.g. radical cystectomy), performed within the last 120 days * Must have disease free status as determined by imaging within 4 weeks of dosing * Tumor tissue must be provided for biomarker analysis * Patients who have not received prior neoadjuvant cisplatin chemotherapy must be ineligible for or refuse cisplatin-based adjuvant chemotherapy
Exclusion criteria
* Partial bladder or partial kidney removal (eg, partial cystectomy or partial nephrectomy) * Secondary Treatment (eg, adjuvant systemic chemotherapy for bladder cancer) following surgical removal of bladder cancer * Subjects with active, known or suspected autoimmune disease * Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured * Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 day of study drug administration * Positive test for hepatitis B virus surface antigen (HBV s Ag) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | approximately up to 48 months | The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first. |
| Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population | approximately up to 48 months | The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Non-Urothelial Tract Recurrence Free Survival | up to 53 months | The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first. |
| Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population | up to 53 months | The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first. |
| Overall Survival | on going | the time from randomization to the date of death from any cause. |
| Overall Survival in Participants With PD-L1 Expression ≥ 1% | on going | the time from randomization to the date of death from any cause. |
| Disease Specific Survival | on going | the time from randomization to the date of death due to disease (urothelial cancer). |
| Disease Specific Survival in Participants With PD-L1 Expression ≥ 1% | on going | the time from randomization to the date of death due to disease (urothelial cancer). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, France, Germany, Greece, Ireland, Israel, Italy, Japan, Mexico, Netherlands, Peru, Poland, Romania, Russia, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
709 Participants Randomized, 699 Treated
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 356 |
| Nivolumab Nivolumab 240mg IV Q2W | 353 |
| Total | 709 |
Baseline characteristics
| Characteristic | Nivolumab | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 65.3 Years STANDARD_DEVIATION 10.1 | 65.6 Years STANDARD_DEVIATION 9.5 | 65.9 Years STANDARD_DEVIATION 8.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 37 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 285 Participants | 143 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 195 Participants | 387 Participants | 192 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 80 Participants | 155 Participants | 75 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) White | 264 Participants | 536 Participants | 272 Participants |
| Sex: Female, Male Female | 88 Participants | 169 Participants | 81 Participants |
| Sex: Female, Male Male | 265 Participants | 540 Participants | 275 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 307 / 348 | 332 / 351 |
| serious Total, serious adverse events | 129 / 348 | 122 / 351 |
Outcome results
Primary
Disease Free Survival (DFS)
The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
Time frame: approximately up to 48 months
Population: All Randomized Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Disease Free Survival (DFS) | 10.84 Months |
| Nivolumab | Disease Free Survival (DFS) | 20.76 Months |
p-value: 0.000898.22% CI: [0.55, 0.9]Stratified Cox Proportional hazard model
Primary
Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population
The time between the date of randomization and the date of first documented recurrence (local urothelial tract, local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
Time frame: approximately up to 48 months
Population: All Randomized Participants with PD-L1 expression ≥ 1%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population | 8.41 Months |
| Nivolumab | Disease Free Survival (DFS) in PD-L1 Expression ≥ 1% Population | NA Months |
p-value: 0.000598.72% CI: [0.35, 0.84]Stratified Cox Proportional hazard model
Secondary
Disease Specific Survival
the time from randomization to the date of death due to disease (urothelial cancer).
Time frame: on going
Secondary
Disease Specific Survival in Participants With PD-L1 Expression ≥ 1%
the time from randomization to the date of death due to disease (urothelial cancer).
Time frame: on going
Secondary
Non-Urothelial Tract Recurrence Free Survival
The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
Time frame: up to 53 months
Population: All Randomized Participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Non-Urothelial Tract Recurrence Free Survival | 13.70 Months |
| Nivolumab | Non-Urothelial Tract Recurrence Free Survival | 22.93 Months |
Secondary
Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population
The time between the date of randomization and the date of first documented recurrence (local non-urothelial tract or distant), or death due to any cause, whichever occurs first.
Time frame: up to 53 months
Population: All Randomized Participants with PD-L1 expression ≥ 1%
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population | 10.84 Months |
| Nivolumab | Non-Urothelial Tract Recurrence Free Survival in PD-L1 Expression ≥ 1% Population | NA Months |
Secondary
Overall Survival
the time from randomization to the date of death from any cause.
Time frame: on going
Secondary
Overall Survival in Participants With PD-L1 Expression ≥ 1%
the time from randomization to the date of death from any cause.
Time frame: on going