Urinary Bladder Neoplasms
Conditions
Brief summary
A study comparing nivolumab and bacterial drugs given to help the body's immune system in the bladder versus bacterial drugs alone in high risk bladder cancer participants.
Interventions
DRUGnivolumab
Specified Dose on Specified Days
OTHERPlacebo
Specified Dose on Specified Days
BIOLOGICALBacillus Calmette-Guérin (BCG)
Specified Dose on Specified Days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Persistent or recurrent disease ≤ 24 months of last BCG dose, but not classified as BCG unresponsive * Histologically confirmed persistent or recurrent high-risk non-muscle-invasive urothelial carcinoma (UC) * Treated with at least 1 adequate course of induction BCG therapy (at least 5 out of 6 doses) * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
Exclusion criteria
* Previous or concurrent muscle invasive, locally advanced, or disseminated/metastatic UC * UC in the upper genitourinary tract (kidneys, renal collecting systems, ureters) within 24 months of enrollment * UC and/or CIS in the prostatic urethra within 12 months of enrollment Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Event Free Survival | Approximately 44 Months and 1 Week | The time between the date of randomization and the date of first documented event or death due to any cause, whichever occurs first. Events include recurrence of disease (TaHG, T1, or CIS) and progression of disease. Data Not Collected (DNC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Overall Survival | Approximately 44 months and 1 week | The time between the date of randomization and the date of death due to any cause. For participants still alive, OS is censored at the last date the participant is known to be alive. Data Not Collected (DNC) |
| Part 2: Complete Response Rate at 13 Weeks | 13 Weeks | CRR is defined as the proportion of participants with CIS (+/- TaHG/T1) per PRC at randomization who are disease free at the first disease assessment (Week 13) Data Not Collected (DNC) |
| Part 2: Duration of Response | Approximately 44 months and 1 week | the time between the date of the first CR to the date of first documented recurrence, progression, or death due to any cause. Data Not Collected (DNC) |
| Part 2: Worsening-Free Survival | Approximately 44 months and 1 week | The time from randomization to progression to muscle-invasive disease (ie, T2), cystectomy, systemic chemotherapy, radiotherapy, or death from any cause. Data Not Collected (DNC) |
| All-causality Adverse Events | 24.6 months | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria. |
| Drug-related Adverse Events | 24.6 months | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria. |
| All-causality Adverse Events Leading to Discontinuation | 24.6 months | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, France, Germany, Greece, Israel, Italy, Netherlands, Russia, Spain, Sweden, United States
Participant flow
Pre-assignment details
Study terminated shortly after phase 1 (safety period), phase 2 efficacy period did not initiate.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Nivolumab 480 mg intravenous (IV) every 4 weeks (Q4W) for up to 24 months (104 weeks) and intravesical BCG (induction) weekly for 6 weeks followed by maintenance intravesical BCG weekly for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months | 8 |
| Arm B Nivolumab-placebo IV Q4W for up to 24 months (104 weeks) and intravesical BCG (induction) weekly for 6 weeks followed by maintenance intravesical BCG weekly for 3 weeks at 3, 6, 12, 18, 24, 30, and 36 months | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Arm B | Total | Arm A |
|---|---|---|---|
| Age, Continuous | 73.0 Years STANDARD_DEVIATION 15.3 | 65.1 Years STANDARD_DEVIATION 12.6 | 61.1 Years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 6 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 11 Participants | 7 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 10 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 4 |
| other Total, other adverse events | 5 / 8 | 4 / 4 |
| serious Total, serious adverse events | 2 / 8 | 0 / 4 |
Outcome results
Primary
Part 2: Event Free Survival
The time between the date of randomization and the date of first documented event or death due to any cause, whichever occurs first. Events include recurrence of disease (TaHG, T1, or CIS) and progression of disease. Data Not Collected (DNC)
Time frame: Approximately 44 Months and 1 Week
Population: Study terminated. Data Not Collected. Study was terminated due to slow enrollment. Decision was made to terminate study before entering phase 2 (efficacy portion).
Secondary
All-causality Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria.
Time frame: 24.6 months
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | All-causality Adverse Events | Grade 1 | 1 Participants |
| Arm A | All-causality Adverse Events | Grade 2 | 4 Participants |
| Arm A | All-causality Adverse Events | Grade 3 | 1 Participants |
| Arm B | All-causality Adverse Events | Grade 3 | 1 Participants |
| Arm B | All-causality Adverse Events | Grade 1 | 2 Participants |
| Arm B | All-causality Adverse Events | Grade 2 | 1 Participants |
Secondary
All-causality Adverse Events Leading to Discontinuation
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria.
Time frame: 24.6 months
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | All-causality Adverse Events Leading to Discontinuation | Any Grade | 1 Participants |
| Arm A | All-causality Adverse Events Leading to Discontinuation | Grade 3-4 | 0 Participants |
| Arm A | All-causality Adverse Events Leading to Discontinuation | Grade 5 | 0 Participants |
| Arm B | All-causality Adverse Events Leading to Discontinuation | Any Grade | 3 Participants |
| Arm B | All-causality Adverse Events Leading to Discontinuation | Grade 3-4 | 0 Participants |
| Arm B | All-causality Adverse Events Leading to Discontinuation | Grade 5 | 0 Participants |
Secondary
Drug-related Adverse Events
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Grading will be based on NCI CTCAE version 5.0 criteria.
Time frame: 24.6 months
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A | Drug-related Adverse Events | Grade 1 | 1 Participants |
| Arm A | Drug-related Adverse Events | Grade 2 | 4 Participants |
| Arm A | Drug-related Adverse Events | Grade 3 | 1 Participants |
| Arm B | Drug-related Adverse Events | Grade 1 | 1 Participants |
| Arm B | Drug-related Adverse Events | Grade 2 | 1 Participants |
| Arm B | Drug-related Adverse Events | Grade 3 | 1 Participants |
Secondary
Part 2: Complete Response Rate at 13 Weeks
CRR is defined as the proportion of participants with CIS (+/- TaHG/T1) per PRC at randomization who are disease free at the first disease assessment (Week 13) Data Not Collected (DNC)
Time frame: 13 Weeks
Population: Study terminated. Data Not Collected. Study was terminated due to slow enrollment. Decision was made to terminate study before entering phase 2 (efficacy portion).
Secondary
Part 2: Duration of Response
the time between the date of the first CR to the date of first documented recurrence, progression, or death due to any cause. Data Not Collected (DNC)
Time frame: Approximately 44 months and 1 week
Population: Study terminated. Data Not Collected. Study was terminated due to slow enrollment. Decision was made to terminate study before entering phase 2 (efficacy portion).
Secondary
Part 2: Overall Survival
The time between the date of randomization and the date of death due to any cause. For participants still alive, OS is censored at the last date the participant is known to be alive. Data Not Collected (DNC)
Time frame: Approximately 44 months and 1 week
Population: Study terminated. Data Not Collected. Study was terminated due to slow enrollment. Decision was made to terminate study before entering phase 2 (efficacy portion).
Secondary
Part 2: Worsening-Free Survival
The time from randomization to progression to muscle-invasive disease (ie, T2), cystectomy, systemic chemotherapy, radiotherapy, or death from any cause. Data Not Collected (DNC)
Time frame: Approximately 44 months and 1 week
Population: Study terminated. Data Not Collected. Study was terminated due to slow enrollment. Decision was made to terminate study before entering phase 2 (efficacy portion).