Bladder Cancer
Conditions
Keywords
Intravesical BCG, Bacille Calmette-Guerin, avelumab
Brief summary
The purpose of this study is to test the safety of avelumab and Bacille Calmette-Guerin (BCG) and see what effects (good and bad) that this combination treatment has on subjects with recurrent bladder cancer.
Detailed description
There will be exams, tests and procedures to see if the patient is eligible for the study. Some are part of regular cancer care and others are part of the study. Subjects will also need to complete a research questionnaire at certain points in the study. Subjects will receive treatment of avelumab and intravesical BCG until unacceptable toxicity or tumor progression. Study participation is up to three years.
Interventions
DRUGAvelumab
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
BIOLOGICALBCG
Induction phase (cycle 1): • Once weekly for weeks 1-6 Maintenance phase (Month 3, 6, and 12): • Once weekly for 3 weeks
Sponsors
EMD Serono
University of Oklahoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically documented Non-muscle Invasive Bladder Cancer (NMIBC) 2. Patient with BCG-treated but unresponsive NMIBC (persistent or recurrent defined as tumor lesion present after prior response). 3. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 2. 4. Patients who are able to understand and sign the informed consent form. 5. Age ≥ 18 years old 6. Ability to comply with protocol 7. Life expectancy \>/=12 weeks 8. Adequate hematologic and end-organ function per protocol 9. For women of childbearing potential: Negative serum or urine pregnancy test at screening. 10. For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of \<1% per year during the treatment period and for at least 30 days after the last dose of study drug.
Exclusion criteria
1. Evidence of locally advanced or metastatic bladder cancer (including current disease involving renal pelvis, ureter, or prostatic urethra). 2. Evidence of muscle-invasive bladder cancer 3. Evidence of extravesical bladder cancer 4. Active central nervous system (CNS) metastases. 5. Prior treatment with PD-L1 or PD-1 inhibitor. 6. Prior radiation to bladder 7. Known additional malignancy that required active treatment within the last 2 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin. 8. Patient is considered a poor medical risk that would interfere with cooperation with the requirements of the study. 9. Patient has a condition or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment. 10. Patient has not recovered (i.e, to ≤Grade 1 or to baseline) from previous intravesical BCG or other anti-cancer therapy induced AEs. 11. Treatment with any approved anti-cancer therapy, including chemotherapy (systemic or intravesical), radiation therapy, or hormonal therapy within 3 weeks prior to the first dose of study treatment 12. Treatment with any other investigational agent or participation in another clinical study with therapeutic intent within 4 weeks prior to the first dose of study treatment 13. Pregnant or lactating, or intending to become pregnant during the study a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to the first dose of study treatment. 14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins 15. Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells 16. Allergy or hypersensitivity to components of the avelumab formulation 17. History of autoimmune disease defined per protocol 18. Prior allogeneic stem cell or solid organ transplantation 19. Current use of immunosuppressive medication defined per protocol 20. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 21. Positive test for HIV 22. Active hepatitis B (positive hepatitis B surface antigen \[HBsAg\] test at screening); a. Patients with past or resolved hepatitis B (HBV) infection (positive anti-hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. HBV DNA must be obtained in these patients prior to the first dose of study treatment. 23. Active hepatitis C a. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction assay is negative for HCV RNA. 24. Active infection requiring systemic therapy 25. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia 26. Significant cardiovascular disease, such as cerebral vascular accident/stroke (\< 6 months prior to enrollment), New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina 27. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study 28. Other severe acute or chronic medical conditions defined per protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Receiving Complete Induction Course | 8 weeks | Proportion of patients receiving complete induction course, defined as freedom from DLT preventing completion of at least 5 of 6 treatments of BCG + avelumab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Patients With Complete Response | 3 months | based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response. |
| Proportion of Patients With Complete Response | 6 months | based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response. |
| Proportion of Patients Receiving Complete Induction Course | 5 weeks | completion of at least 2 of 3 treatments within each 5 week period |
| Proportion of Patients With Recurrence Free Survival | 12 months | defined as proportion of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy |
| Proportion of Patients With Progression-free Survival | 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 |
| Percent of Patients With Recurrence Free Survival | 6 months | defined as percent of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | BCG + Avelumab |
|---|---|
| Age, Continuous | 69.94 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 11 / 18 |
Outcome results
Primary
Proportion of Patients Receiving Complete Induction Course
Proportion of patients receiving complete induction course, defined as freedom from DLT preventing completion of at least 5 of 6 treatments of BCG + avelumab
Time frame: 8 weeks
Population: Patients who enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients Receiving Complete Induction Course | 0.833 proportion of patients |
Secondary
Percent of Patients With Complete Response
based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response.
Time frame: 3 months
Population: Patients who enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Percent of Patients With Complete Response | 17.6 percent of patients |
Secondary
Percent of Patients With Recurrence Free Survival
defined as percent of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy.
Time frame: 6 months
Population: Patients who experienced complete response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Percent of Patients With Recurrence Free Survival | 88.89 percent of patients |
Secondary
Proportion of Patients Receiving Complete Induction Course
completion of at least 2 of 3 treatments within each 5 week period
Time frame: 5 weeks
Population: Patients who remained on study for induction course
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients Receiving Complete Induction Course | 0.9091 proportion |
Secondary
Proportion of Patients With Complete Response
based on negative cystoscopy and urine cytology. A negative biopsy at 6 months will provide evidence of complete response.
Time frame: 6 months
Population: Patients who enrolled in study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients With Complete Response | 41.2 percent |
Secondary
Proportion of Patients With Progression-free Survival
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
Time frame: 6 months
Population: Patients who experienced progression or death or who stayed on study for at least 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients With Progression-free Survival | 0.8824 proportion of patients |
Secondary
Proportion of Patients With Progression-free Survival
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
Time frame: 12 months
Population: Patients who experienced progression or death or who remained at study at least 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients With Progression-free Survival | 0.8145 proportion of patients |
Secondary
Proportion of Patients With Recurrence Free Survival
defined as proportion of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy
Time frame: 12 months
Population: Patients who experienced complete response
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BCG + Avelumab | Proportion of Patients With Recurrence Free Survival | 0.8889 proportion of patients |