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

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

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.

Study Overview

• Status: Completed
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Avelumab; Biological: BCG

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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; Other Names: Bacille Calmette-Guérin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Receiving Complete Induction Course	completion of at least 2 of 3 treatments within each 5 week period	5 weeks
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: EMD Serono
• Investigators: Principal Investigator: Kelly Stratton, MD, Stephenson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): March 23, 2021
• Study Completion (Actual): August 13, 2023

Study Registration Dates

• First Submitted: February 7, 2019
• First Submitted That Met QC Criteria: March 25, 2019
• First Posted (Actual): March 27, 2019

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Intravesical BCG; avelumab; Bacille Calmette-Guerin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Avelumab
• Other Study ID Numbers: OU-SCC-ABC (Other Grant/Funding Number: EMD Serono)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No