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Afatinib Dimaleate in Treating Patients with Advanced Refractory Urothelial Cancer

Trial Status: Active

This phase II trial studies how well afatinib dimaleate works in treating patients with urothelial cancer that has not responded to previous treatment (refractory). Afatinib dimaleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Inclusion Criteria

  • Patients must have locally advanced or metastatic urothelial cancer that is not amenable to surgical treatment
  • Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan for the evaluation of measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1])
  • Patients must have evidence of disease progression prior to enrollment
  • All patients must have received a prior platinum-based chemotherapy regimen for treatment of urothelial cancer and must now be considered refractory to platinum-based chemotherapy; patients may have received the platinum-containing regimen either in the peri-operative or metastatic setting; patients may have received any number of additional prior therapies, and may have received prior immune therapies
  • Patients must have tumor evidence of somatic genomic molecular alteration in EGFR, HER2, ERBB3, or ERBB4, from a test result generated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; the tumor tissue sample used to generate the qualifying report must be from a muscle-invasive or higher stage urinary tract cancer specimen (metastatic tissue is also acceptable); final determination about whether a specific tissue source or molecular genomic finding meets criteria as a qualifying result rests with the central study principal investigator (PI); germline genomic findings will not be returned to patients
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.5 g/dL
  • Total bilirubin =< 1.5 institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X IULN
  • Calculated creatinine clearance >= 30 mL/min by the modified Cockcroft and Gault formula OR glomerular filtration rate >= 30 mL/min/body surface area (BSA) by Modification of Diet in Renal Disease or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
  • Women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients must have the ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

  • Patients may not be receiving any other investigational agents
  • Patients with untreated known brain metastases, or treated brain metastases that are clinically unstable
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
  • Women known to be pregnant
  • Women who are breastfeeding and who are unwilling to stop breastfeeding prior to study entry
  • Patients with known prior human immunodeficiency virus (HIV)-positive status on combination antiretroviral therapy are ineligible; known prior HIV-positive patients with cluster of differentiation (CD)4+ =< 500/mm^3 are ineligible (HIV testing is not required as part of this study)
  • Pre-existing interstitial lung disease
  • Inability to take oral medications
  • Prior therapy with afatinib


University of Chicago Comprehensive Cancer Center
Status: ACTIVE
Contact: Peter H. O'Donnell
Phone: 773-702-7564
Decatur Memorial Hospital
Status: ACTIVE
Contact: James Lloyd Wade
NorthShore University HealthSystem-Evanston Hospital
Contact: Daniel H. Shevrin
Phone: 847-570-2515

New York

New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone
Status: ACTIVE
Contact: Arjun V. Balar

North Carolina

Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: ACTIVE
Contact: Matthew Ivan Milowsky
Phone: 919-843-7942


I. To determine the 6-month progression free survival (PFS) rate of molecularly-selected metastatic urothelial cancer patients treated with afatinib dimaleate (afatinib) who have progressed despite prior platinum-based chemotherapy.


I. To determine the overall response rate (complete response [CR] + partial response [PR]), median progression free survival, and overall survival for the same treated population.

II. To examine the role of different ErBB alterations in determining afatinib activity in urothelial cancer.


I. To determine whether tumor EGFR and/or HER2 expression, or, alternatively, whether certain micro ribonucleic acid (RNA)s, influence 6-month PFS in patients treated with afatinib.


Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-56. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 3 years.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of Chicago Comprehensive Cancer Center

Principal Investigator
Peter H. O'Donnell

  • Primary ID IRB13-0540
  • Secondary IDs NCI-2014-00859, 13-0540
  • ID NCT02122172