Clinical Trials /

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

NCT03892642

Description:

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.

Related Conditions:
  • Bladder Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: OUSCC-ABC
  • NCT ID: NCT03892642

Conditions

  • Bladder Cancer

Interventions

DrugSynonymsArms
AvelumabBCG + Avelumab
BCGBacille Calmette-GuérinBCG + Avelumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
BCG + AvelumabExperimentalCombination 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
  • BCG

Eligibility Criteria

        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

        Exclusion Criteria:

          1. Evidence of locally advanced or metastatic bladder cancer (including 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 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients receiving complete induction course
Time Frame:8 weeks
Safety Issue:
Description:defined as freedom from DLT preventing completion of at least 5 of 6 treatments of BCG + avelumab

Secondary Outcome Measures

Measure:Proportion of patients receiving complete induction course
Time Frame:5 weeks
Safety Issue:
Description:completion of at least 2 of 3 treatments within each 5 week period
Measure:Proportion of patients with Complete Response
Time Frame:3 months
Safety Issue:
Description:based on negative cystoscopy and urine cytology
Measure:Proportion of patients with Complete Response
Time Frame:6 months
Safety Issue:
Description:based on negative cystoscopy and urine cytology
Measure:Proportion of patients with recurrence free survival
Time Frame:6 months
Safety Issue:
Description:defined as proportion of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy
Measure:Proportion of patients with recurrence free survival
Time Frame:12 months
Safety Issue:
Description:defined as proportion of patients who are alive and free of persistent or recurrent NMIBC based on cystoscopy, cytology and/or biopsy
Measure:Proportion of patients with Progression-free survival
Time Frame:6 months
Safety Issue:
Description: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
Measure:Proportion of patients with Progression-free survival
Time Frame:12 months
Safety Issue:
Description: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
Measure:Survival curves of cystectomy-free survival
Time Frame:Up to three years
Safety Issue:
Description:defined as time from study initiation to cystectomy or death
Measure:Survival curves of overall survival
Time Frame:Up to three years
Safety Issue:
Description:defined as time from day of first treatment to death from any cause

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Oklahoma

Trial Keywords

  • Intravesical BCG
  • Bacille Calmette-Guerin
  • avelumab

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