Trial Outcomes & Findings for Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer (NCT NCT03892642)
NCT ID: NCT03892642
Last Updated: 2024-02-14
Results Overview
Proportion of patients receiving complete induction course, defined as freedom from DLT preventing completion of at least 5 of 6 treatments of BCG + avelumab
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
8 weeks
Results posted on
2024-02-14
Participant Flow
Recruitment for the Stephenson Cancer Center began in May 2019, with the first patient consenting, and last patient consent occurred in February 2021. The Stephenson Cancer is no longer recruiting for this study as all the slots have been filled and subjects accrued per protocol.
Participant milestones
| Measure |
BCG + Avelumab
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Overall Study
STARTED
|
18
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer
Baseline characteristics by cohort
| Measure |
BCG + Avelumab
n=18 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Age, Continuous
|
69.94 years
STANDARD_DEVIATION 9.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Patients who enrolled in study
Proportion of patients receiving complete induction course, defined as freedom from DLT preventing completion of at least 5 of 6 treatments of BCG + avelumab
Outcome measures
| Measure |
BCG + Avelumab
n=18 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients Receiving Complete Induction Course
|
0.833 proportion of patients
Interval 0.5774 to 0.9559
|
SECONDARY outcome
Timeframe: 5 weeksPopulation: Patients who remained on study for induction course
completion of at least 2 of 3 treatments within each 5 week period
Outcome measures
| Measure |
BCG + Avelumab
n=11 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients Receiving Complete Induction Course
|
0.9091 proportion
Interval 0.5712 to 0.9952
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Patients who enrolled in study
based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response.
Outcome measures
| Measure |
BCG + Avelumab
n=18 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Percent of Patients With Complete Response
|
17.6 percent of patients
Interval 3.8 to 43.4
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Patients who enrolled in study
based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response.
Outcome measures
| Measure |
BCG + Avelumab
n=18 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients With Complete Response
|
41.2 percent
Interval 18.4 to 67.1
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Patients who experienced complete response
defined as percent of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy.
Outcome measures
| Measure |
BCG + Avelumab
n=9 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Percent of Patients With Recurrence Free Survival
|
88.89 percent of patients
Interval 43.29 to 98.36
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Patients who experienced complete response
defined as proportion of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy
Outcome measures
| Measure |
BCG + Avelumab
n=9 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients With Recurrence Free Survival
|
0.8889 proportion of patients
Interval 0.4329 to 0.9836
|
SECONDARY outcome
Timeframe: 6 monthsPopulation: Patients who experienced progression or death or who stayed on study for at least 6 months
defined by time from day of first treatment to first progression to higher grade or stage, including muscle-invasive disease or death from any cause
Outcome measures
| Measure |
BCG + Avelumab
n=17 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients With Progression-free Survival
|
0.8824 proportion of patients
Interval 0.6059 to 0.9692
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Patients who experienced progression or death or who remained at study at least 12 months
defined by time from day of first treatment to first progression to higher grade or stage, including muscle-invasive disease or death from any cause
Outcome measures
| Measure |
BCG + Avelumab
n=15 Participants
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Proportion of Patients With Progression-free Survival
|
0.8145 proportion of patients
Interval 0.5263 to 0.9364
|
Adverse Events
BCG + Avelumab
Serious events: 11 serious events
Other events: 18 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
BCG + Avelumab
n=18 participants at risk
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Cardiac disorders
Atrial flutter
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Diarrhea
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
General disorders
Non-cardiac chest pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Infections and infestations
Lung infection
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Infections and infestations
Sepsis
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
Cardiac troponin I increased
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Nervous system disorders
Depressed level of consciousness
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Nervous system disorders
Myasthenia gravis
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
Other adverse events
| Measure |
BCG + Avelumab
n=18 participants at risk
Combination of avelumab and intravesical BCG. One cycle = 12 weeks (84 days). A standard maintenance therapy regimen will be provided with BCG occurring at Month 3, 6, and 12. Avelumab treatment ends at the conclusion of Month 12 maintenance therapy.
Avelumab: Induction phase:
* once weekly for weeks 1-6,
* once every 2 weeks at week 8, 10, and 12
Maintenance phase:
* Once every week for weeks 1-3
* Once every 2 weeks starting at week 5, until the next BCG treatment
BCG: Induction phase (cycle 1):
• Once weekly for weeks 1-6
Maintenance phase (Month 3, 6, and 12):
• Once weekly for 3 weeks
|
|---|---|
|
Ear and labyrinth disorders
Vertigo
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Endocrine disorders
Hyperthyroidism
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Endocrine disorders
Hypothyroidism
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Eye disorders
Blurred vision
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Abdominal pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Constipation
|
16.7%
3/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Dental caries
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Diarrhea
|
16.7%
3/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Dry mouth
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Mucositis oral
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Nausea
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Other SpecifyDiverticulitis
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Gastrointestinal disorders
Vomiting
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
General disorders
Chills
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
General disorders
Fatigue
|
33.3%
6/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
General disorders
Flu like symptoms
|
22.2%
4/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
General disorders
Infusion site extravasation
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Infections and infestations
Penile infection
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Infections and infestations
Shingles
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Infections and infestations
Urinary tract infection
|
38.9%
7/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Injury, poisoning and procedural complications
Bruising
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
27.8%
5/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
Activated partial thromboplastin time prolonged
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
CPK increased
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
Cardiac troponin I increased
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
Creatinine increased
|
22.2%
4/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Investigations
Thyroid stimulating hormone increased
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Psychiatric disorders
Insomnia
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Bladder spasm
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Dysuria
|
61.1%
11/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Hematuria
|
27.8%
5/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Other SpecifyNOCTURIA
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Other SpecifyUrinary Disorder
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Renal calculi
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Urinary frequency
|
55.6%
10/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Urinary retention
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Urinary tract obstruction
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Renal and urinary disorders
Urinary urgency
|
27.8%
5/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Reproductive system and breast disorders
Other Specify
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Reproductive system and breast disorders
Penile pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Reproductive system and breast disorders
Prostatic pain
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
5.6%
1/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
|
Vascular disorders
Hypertension
|
11.1%
2/18 • 2 years, 9 months
AEs graded according to CTCAE v 5.0
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place