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Avelumab for the Treatment of Muscle Invasive Bladder Cancer

Trial Status: Active

This early phase I trial studies how well avelumab works in treating patients with muscle invasive bladder cancer. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Specifically, avelumab may increase the body’s ability to fight cancer with anti-tumor white blood cells called lymphocytes. Avelumab may have an effect on the cancer, but it is not yet known if the planned treatment duration is long enough to control the cancer.

Inclusion Criteria

  • Have undergone transurethral resection of the bladder tumor (TURBT) showing newly diagnosed muscle invasive urothelial cancer of the bladder (UCB) (mixed histology is allowed if the predominant histology is urothelial cell carcinoma [UCC]) within 6 weeks prior to cycle 1, day 1 of treatment
  • No prior systemic treatment for muscle invasive UCB
  • Clinical T2-T4a disease
  • No evidence of clinically positive lymph nodes or distant metastasis on computed tomography (CT) scans of chest and CT or magnetic resonance imaging (MRI) studies of the abdomen/pelvis. Imaging must be within 90 days of registration
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 30 days of registration)
  • Platelet count >= 100 x 10^9/L (within 30 days of registration)
  • Hemoglobin >= 9 g/dL (may have been transfused) (within 30 days of registration)
  • Total bilirubin level =< 1.5 x upper limit of normal (ULN) (within 30 days of registration)
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =< 2.5 x ULN (within 30 days of registration)
  • Estimated creatinine clearance >= 30 mL/min according to the Cockcroft-Gault formula (within 30 days of registration)
  • Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP), within 30 days of registration
  • Both male and female subjects must agree to use highly effective contraception while receiving avelumab and for at least 60 days after last avelumab treatment if the risk of conception exists. * Female patients must agree to inform study coordinator or investigator immediately if they think they have become pregnant during the study
  • Must have FFPE tissue available from the TURBT, and patient must consent to the use of tissue specimens from TURBT and radical cystectomy (RC) for the study
  • Patients must be ineligible for cisplatin-based neoadjuvant chemotherapy (NAC). Ineligibility criteria include: creatinine clearance < 60 ml/min by Cockcroft-Gault formula, Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 hearing loss, CTCAE grade >= 2 neuropathy, and at discretion of medical oncologist
  • Must be eligible for RC in the opinion of the treating investigator, and willing to undergo this procedure
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-2
  • Signed informed consent form

Exclusion Criteria

  • Current use of immunosuppressive medication or within 4 weeks of cycle 1 day 1 (C1D1), EXCEPT for the following: * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses =< 10 mg/day of prednisone or equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • 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. Patients with type I diabetes or hypo- or hyperthyroidism should be on stable doses of medications for participation
  • Prior organ transplantation including allogenic stem-cell transplantation
  • Active infection requiring systemic therapy
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
  • 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)
  • Vaccinate within 4 weeks of the first dose of avelumab and while on study drug is prohibited except for administration of inactivated vaccines
  • Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute [NCI] CTCAE version [v]4.03 grade >= 3)
  • Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (>= New York Heart Association Classification class II), or serious cardiac arrhythmia requiring medication
  • Other severe acute or chronic medical conditions including colitis, inflammatory bowel disease, 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
  • Relapsed muscle invasive bladder cancer (MIBC) (all patients participating in the study should be newly diagnosed)
  • Concomitant UCC outside the bladder (e.g., ureter, urethra or renal pelvis)
  • Underlying immune disorder (e.g., combined variable immunodeficiency syndrome)
  • Erythropoietin receptor agonists within 30 days prior to enrollment
  • Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) or thrombopoietin (TPO) mimetics during the study period or within 3 weeks prior to study enrollment
  • Malignancies other than UCB within 5 years prior to cycle 1, day 1, with the exception of those with low risk of metastasis or death treated with expected curative outcome (such as, but not limited to, adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent and absence of PSA relapse, or ductal carcinoma in situ of the breast treated surgically with curative intent) or incidental prostate cancer (T1a, Gleason score =< 6 and PSA < 0.5 ng/ml)
  • Prior immunotherapy with T-cell co-stimulation or checkpoint targeted agents (e.g., CTLA-4 inhibitors, anti-PD1 antibodies or anti-PD-L1 antibodies)
  • Intravesical chemotherapy or biologic therapy within 6 weeks of cycle 1, day 1
  • Current participation in another clinical trial for MIBC
  • Nursing or pregnant woman
  • Uncontrolled cystitis, significant bladder pain or spasms, or gross hematuria that in the opinion of the principal investigator will preclude study participation
  • Major surgical procedures within 4 weeks of registration (other than for diagnosis) or anticipation that such a procedure will be needed during the study (other than RC)


Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Jennifer Marie Taylor
Phone: 713-798-7670
Ben Taub General Hospital
Status: ACTIVE
Contact: Jennifer Marie Taylor
Phone: 713-798-7670
Michael E DeBakey VA Medical Center
Status: ACTIVE
Contact: Jennifer Marie Taylor
Phone: 713-798-7670


I. To evaluate change in T cell subpopulations (CD8, CD4 and/or CD3) in tumor samples collected pre- and post-treatment with avelumab.


I. To evaluate pathologic partial response (downstaging to < pT2) and complete response.

II. To evaluate 2 year disease free survival (DFS).

III. To evaluate safety of drug in the neoadjuvant (NA) setting.

IV. To evaluate correlation of translational studies with response parameters.


I. To evaluate PD-L1 by immunohistochemistry (IHC) and COX-1/COX-2 expression by messenger ribonucleic acid (mRNA) in pre- treatment cancer tissues (focusing on epithelial cell expression and immune cell expression).

II. To evaluate infiltrating CD3+, CD4+ and CD3+, CD8+ T cells in pre- and post- PD-L1 antibody treated patient cancer tissues by IHC.

III. To evaluate change in regulatory B-cell populations with treatment as identified by IHC for CD1d, CD5, CD19 and CD24.

IV. To evaluate mRNA levels of the following chemokines/cytokines and immune checkpoints on formalin fixed paraffin embedded (FFPE) tissue from pre- and post-treatment specimens: IFN-gamma, TNF-alpha, TNF-veta, T-box protein in B-cells (T-bet), IL-2, IL10, IL-35, FOXP-3, CTLA-4, LAG-3, PD-L1, granzyme-A and perforin-1.


Patients receive avelumab intravenously (IV) over 60 minutes on day 1. Treatment repeats every 14 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Within 5 weeks after completing avelumab, patients undergo radical cystectomy.

After completion of study, patients are followed up at 2-3 weeks, 30, 60, and 90 days, and every 3 months for up to 2 years post-operative.

Trial Phase Phase O

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Jennifer Marie Taylor

  • Primary ID BL-AIR H-41207
  • Secondary IDs NCI-2019-01959
  • ID NCT03498196