Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer

Bladder Cancer Clinical Trial

— OU-SCC-ABC  

Official title:

Phase Ib Study of Avelumab Plus Bacille Calmette-Guerin (BCG) in Patients With Non-muscle Invasive Bladder Cancer (ABC Trial)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03892642
• Other study ID #: OU-SCC-ABC
• Secondary ID: OU-SCC-ABC
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: May 1, 2019
• Est. completion date: August 13, 2023

Study information

• Verified date: February 2024
• Source: University of Oklahoma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: August 13, 2023
• Est. primary completion date: March 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bladder Cancer
• Urinary Bladder Neoplasms

Intervention

Drug:
• 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

Biological:
• BCG
Induction phase (cycle 1): • Once weekly for weeks 1-6 Maintenance phase (Month 3, 6, and 12): • Once weekly for 3 weeks

Locations

Country	Name	City	State
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
University of Oklahoma	EMD Serono

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	8 weeks
Secondary	Proportion of Patients Receiving Complete Induction Course	completion of at least 2 of 3 treatments within each 5 week period	5 weeks
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.	3 months
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.	6 months
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.	6 months
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	12 months
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	6 months
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	12 months