Clinical Trials /

Avelumab and Radiation in Muscle-Invasive Bladder Cancer

NCT03747419

Description:

This research study is studying the effects of adding a certain type of immunotherapy to standard bladder-directed radiation as a treatment for muscle-invasive urothelial carcinoma of the bladder. The drug in this study is: Avelumab (also known as BAVENCIO®)

Related Conditions:
  • Bladder Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab and Radiation in Muscle-Invasive Bladder Cancer
  • Official Title: A Phase 2 Study of Avelumab in Combination With Bladder-Directed Radiation in Cisplatin-Ineligible Patients With Muscle-Invasive Urothelial Carcinoma of the Bladder

Clinical Trial IDs

  • ORG STUDY ID: 18-464
  • NCT ID: NCT03747419

Conditions

  • Bladder Cancer
  • Muscle Invasive Bladder Cancer

Interventions

DrugSynonymsArms
AvelumabBavencioAvelumab and Bladder-Directed Radiation

Purpose

This research study is studying the effects of adding a certain type of immunotherapy to standard bladder-directed radiation as a treatment for muscle-invasive urothelial carcinoma of the bladder. The drug in this study is: Avelumab (also known as BAVENCIO®)

Detailed Description

      This research study is a Phase II clinical trial. Phase II clinical trials test the safety
      and effectiveness of an investigational drug to learn whether the drug works in treating a
      specific disease. "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved the use of avelumab and
      bladder-directed radiation together for this specific disease but avelumab has been approved
      for other uses.

      While bladder-directed radiation is a standard treatment option for muscle-invasive
      urothelial carcinoma of the bladder, the use of avelumab in combination with bladder
      radiation in patients with urothelial carcinoma of the bladder is investigational. Radiation
      is used in the treatment of muscle-invasive bladder cancer, and avelumab has been approved by
      the FDA in patients with more advanced stages of this disease. Avelumab is a form of
      immunotherapy, which means it is designed to help the immune system fight cancer cells
      together with standard cancer treatments like radiation. Avelumab is currently approved by
      the FDA for the treatment of metastatic Merckel cell carcinoma (mMCC) and platinum-refractory
      metastatic urothelial carcinoma.

      The purpose of this study is to test whether the combination of immunotherapy and bladder
      directed radiation is effective in treating muscle-invasive bladder cancer. The study will
      also measure other outcomes such as participant's overall health and quality of life during
      and after treatment. In addition, the investigators will determine if certain biomarkers are
      correlated with outcomes following treatment with immunotherapy and radiation.
    

Trial Arms

NameTypeDescriptionInterventions
Avelumab and Bladder-Directed RadiationExperimentalAvelumab will be administered every 2 weeks intravenously for 6 doses unless there is unacceptable toxicity Two radiation dose regimens are allowed, and the regimen selected is at the discretion of the treating radiation oncologist
  • Avelumab

Eligibility Criteria

        Subjects must meet all of the following applicable inclusion criteria to participate in the
        study.

        Inclusion Criteria:

          -  Histologically confirmed transitional cell (urothelial) carcinoma of the bladder that
             is invasive into the muscularis propria (≥T2 disease) within 6 months of enrollment
             date. The presence of variant histologies (squamous, adenocarcinoma, micropapillary,
             etc.) is allowed. Note: A prior diagnosis of non-muscle-invasive bladder cancer (≤T1)
             managed with transurethral resection with or without intravesicular therapy (now with
             muscle invasion) is allowed.

          -  Inability to receive cisplatin-based chemotherapy, as defined by creatinine clearance
             <60 ml/min, ECOG PS ≤2, grade 2 or higher hearing loss, NYHA class 3 or higher,
             neuropathy (grade 2 or higher), or patient refusal to receive cisplatin-based
             chemotherapy.

        Additional Inclusion Criteria:

          -  Male or female subjects aged ≥18 years

          -  ECOG performance status ≤2 or Karnofsky score ≥60% (see Appendix A)

          -  Life expectancy of greater than 1 year

          -  Demonstrate normal organ and marrow function

          -  Women of child-bearing age must have a negative serum pregnancy test at screening.

          -  Women of child-bearing potential and men must agree to use a highly effective method
             of contraception (hormonal or barrier method of birth control, or abstinence)
             beginning prior to study entry, for the duration of study participation, and for at
             least 30 days after last avelumab treatment administration if the risk of conception
             exists

          -  Ability to understand and willingness to sign a written informed consent document

        Exclusion Criteria:

          -  Prior intravenous therapy for treatment of bladder cancer

          -  Prior pelvic radiation

          -  Any component of small cell histology in the bladder biopsy

          -  Any concurrent chemotherapy, biologic, or hormonal therapy for cancer treatment

          -  Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal,
             inhaled, topical steroid, or local steroid injection (e.g., intra-articular
             injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone
             or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT
             scan premedication) are allowed.

          -  History of another malignancy within 5 years prior to randomization except for:
             non-muscle-invasive bladder cancer (i.e., ≤T1), completely resected basal cell or
             squamous cell skin cancer, completed resected carcinoma-in-situ of any site, or
             localized prostate cancer managed definitively with a non-radiation based approach.

        Additional Exclusion Criteria:

          -  Evidence of lymph node involvement or metastatic disease on CT of the chest, abdomen,
             and pelvis. To be considered positive, a lymph node must measure >15 mm in short axis.

          -  Clinically significant (i.e. active) cardiovascular disease: symptomatic congestive
             heart failure (≥ New York Heart Association Classification Class II), unstable angina
             pectoris, serious cardiac arrhythmia requiring medication, or CVA/stroke/MI (< 6
             months prior to enrollment)

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v4.03 Grade ≥ 3)

          -  Breast feeding women who are unwilling to stop breastfeeding during treatment and for
             at least one month after the duration of treatment

          -  Patients with known history of testing positive for HIV or known acquired
             immunodeficiency syndrome

          -  Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory
             agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid
             diseases not requiring immunosuppressive treatment are eligible.

          -  Active infection requiring intravenous antibiotic therapy

          -  Vaccination within 4 weeks of the first dose of avelumab and while on trial is
             prohibited except for administration of inactivated vaccines

          -  Major surgery within the last 30 days (with the exception of TURBT).

          -  Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive
             HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)

          -  Prior organ transplantation including allogenic stem-cell transplantation

          -  Patient is unwilling to stop (or wishes to start) taking herbal and natural remedies
             that may have immune-modulating effects during the study period

          -  Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however,
             alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety
             risk based on investigator's judgment are acceptable

          -  Other severe acute or chronic medical conditions including immune colitis,
             inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric
             conditions including recent (within the past year) or active suicidal ideation or
             behavior; or laboratory abnormalities that may increase the risk associated with study
             participation or study treatment administration or may interfere with the
             interpretation of study results and, in the judgment of the investigator, would make
             the patient inappropriate for entry into this study.

          -  Pregnant women are excluded from this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete clinical response rate
Time Frame:3 months
Safety Issue:
Description:Measured by the complete clinical response rate at 3 months following completion of radiation.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:3 years
Safety Issue:
Description:OS
Measure:Progression Free Survival
Time Frame:3 years
Safety Issue:
Description:PFS
Measure:Metastases-free survival
Time Frame:3 years
Safety Issue:
Description:MFS
Measure:Locoregional recurrence rate
Time Frame:3 years
Safety Issue:
Description:LRR

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Bladder Cancer
  • Bladder Carcinoma
  • Carcinoma of Bladder
  • Carcinoma of the Bladder
  • MIBC
  • Muscle Invasive Bladder Cancer
  • Muscle-Invasive Urothelial Carcinoma of the Bladder
  • Immunotherapy
  • Avelumab
  • Radiation and Immunotherapy
  • No cisplatin
  • Cisplatin Ineligible
  • Cisplatin-Ineligible
  • T2 Disease
  • T3 Disease
  • T4 Disease
  • squamous bladder cancer
  • adenocarcinoma bladder cancer
  • micropapillary bladder cancer
  • Inability to receive cisplatin-based chemotherapy

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