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Avelumab and Docetaxel in Treating Patients with Platinum Refractory or Ineligible Metastatic Urothelial Cancer

Trial Status: Temporarily Closed to Accrual

This phase Ib trial studies the best dose of avelumab and how well it works when given together with docetaxel in treating patients with urothelial cancer that has spread to other places in the body and does not respond to platinum chemotherapy or cannot receive platinum chemotherapy. 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. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving avelumab and docetaxel may work better in treating patients with locally advanced or metastatic urothelial cancer.

Inclusion Criteria

  • Histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra). Additional mixed histologies such as squamous, plasmacytoid, adenocarcinoma are permitted provided the urothelial cancer is the predominant histological component
  • Eligible patients must have had either: * Progressed after treatment with at least 1 platinum-containing regimen (e.g., cisplatin or carboplatin plus another agent such as gemcitabine, methotrexate, vinblastine, doxorubicin, etc.) for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence, or * Were ineligible for cisplatin-based chemotherapy, with ineligibility to cisplatin defined by impaired renal function (creatinine clearance < 60 ml/min), a hearing loss of 25 decibels at 2 contiguous frequencies, or grade >= 2 peripheral neuropathy or * Locally advanced or metastatic bladder cancer whose disease has progressed within 12 months of neoadjuvant or adjuvant chemotherapy
  • Biopsy material is required (archival tissue is acceptable if patient could not provide fresh or recent biopsy)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Estimated life expectancy >= 3 months
  • At least one measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • White blood cell count >= 3 x 10^9/L
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Lymphocyte count >= 0.5 x 10^9/L
  • Platelet count >= 100 x 10^9/L
  • Hemoglobin >= 9 g/dL (may have been transfused)
  • Total bilirubin level =< the upper limit of normal range (ULN)
  • An aspartate aminotransferase (AST) level =< 1.5 x ULN
  • An alanine aminotransferase(ALT) level =< 1.5 x ULN
  • Calculated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula
  • Both male and female subjects must be willing to use highly effective contraception (that is, methods with a failure rate of less than 1% per year) throughout the study and for at least 30 days after last avelumab treatment administration if the risk of conception exists * NOTE: The effects of the study treatment on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use highly effective contraception, as stipulated in national or local guidelines. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the treating physician should be informed immediately
  • Signed written informed consent

Exclusion Criteria

  • Concurrent treatment with an anticancer treatment
  • Prior therapy with any drug targeting T cell coregulatory proteins
  • Major surgery for any reason within 4 weeks or if the patient had not fully recovered within 4 weeks
  • Concurrent systemic therapy with corticosteroids or other immunosuppressive agents, or use of any investigational drug within 28 days before starting trial drug; short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-mediated adverse events while on study is allowed
  • Patients with active central nervous metastases will be excluded. Appropriately treated central nervous system (CNS) metastases with either surgery or radiation therapy are permitted to participate in the study
  • Previous malignant disease (other than urothelial carcinoma) within the last 5 years, with the exclusion of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and prostate adenocarcinoma with Gleason score < 7, pT2b
  • Prior organ transplantation, including allogenic stem-cell transplantation
  • Known history of testing positive for human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), hepatitis B virus (HBV), or hepatitis C virus (HCV) (including acute and chronic infection)
  • Active or history of any autoimmune disease or immune-deficiencies (patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible)
  • Known monoclonal antibody hypersensitivity, history of anaphylaxis, or uncontrolled asthma
  • Persisting toxicity related to prior therapy that was > grade 1 according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0; grade =< 2 sensory neuropathy is allowed
  • Pregnancy or lactation
  • 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. All other significant diseases, which in the investigator’s opinion may influence the patient’s tolerance of trial treatment. 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
  • Patients with symptomatic severe chronic obstructive pulmonary disease (COPD) with continuous oxygen requirement will be excluded
  • Legal incapacity or limited legal capacity, including any psychiatric condition that would prohibit the understanding or rendering of informed consent
  • Vaccination within 4 weeks of the first dose of avelumab and while on study was prohibited except for administration of inactivated vaccines (e.g., inactivated influenza vaccines)


Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Contact: Rohan Garje
Phone: 319-356-2075


I. To determine the recommended phase 2 dose (RP2D) of combination therapy with avelumab and docetaxel in subjects with metastatic urothelial cancer. (Phase Ib dose de-escalation)

II. To assess the preliminary efficacy of the established dose of combination therapy with avelumab and docetaxel in subjects with metastatic urothelial cancer. (Phase Ib dose expansion)


I. To evaluate the progression-free survival and overall survival of combination therapy with avelumab and docetaxel in subjects with metastatic urothelial cancer. (Phase Ib dose expansion)


I. Biomarkers: PDL-1 immunostains of the tumor specimen.


INDUCTION: Patients receive avelumab intravenously (IV) over 60 minutes on day 1 and docetaxel IV over 60-90 minutes on day 1. Treatment repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients receive avelumab IV over 60 minutes on day 1. Cycles repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, then every 6 months thereafter.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
Rohan Garje

  • Primary ID 201804833
  • Secondary IDs NCI-2018-02593
  • ID NCT03575013