We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Afatinib in Advanced Refractory Urothelial Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02122172
Recruitment Status : Recruiting
First Posted : April 24, 2014
Last Update Posted : September 28, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Chicago

Brief Summary:
This phase II trial studies how well afatinib dimaleate works in treating patients with urothelial cancer that cannot be removed surgically and has grown after treatment with standard first-line chemotherapy. Afatinib dimaleate may turn off the function of the epidermal growth factor (EGF) and human epidermal growth factor receptor 2 (HER2) receptors, which may slow the growth of cancer cells or cause some of the cells to die.

Condition or disease Intervention/treatment Phase
Distal Urethral Cancer Proximal Urethral Cancer Recurrent Bladder Cancer Recurrent Urethral Cancer Stage III Bladder Cancer Stage III Urethral Cancer Stage IV Bladder Cancer Stage IV Urethral Cancer Ureter Cancer Drug: afatinib dimaleate Other: laboratory biomarker analysis Phase 2

Detailed Description:


I. To determine the 3-month progression free survival (PFS) rate in metastatic urothelial cancer patients receiving afatinib (afatinib dimaleate) 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 determine whether tumor epidermal growth factor receptor (EGFR) and/or HER2 overexpression influences 3-month PFS in patients treated with afatinib.


Patients receive afatinib dimaleate orally (PO) once daily (QD) on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer
Actual Study Start Date : October 30, 2013
Estimated Primary Completion Date : June 12, 2022
Estimated Study Completion Date : June 12, 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (afatinib)
Patients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
Drug: afatinib dimaleate
Given PO
Other Names:
  • afatinib
  • BIBW 2992 MA2
  • Gilotrif

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 3 months ]
    Estimated using the Kaplan-Meier method.

Secondary Outcome Measures :
  1. Overall response rate (CR + PR) [ Time Frame: Up to 3 years ]
  2. Median progression-free survival (PFS ) time [ Time Frame: Up to 3 years ]
    Estimated using the Kaplan-Meier method.

  3. Overall survival [ Time Frame: Up to 3 years ]
    Estimated using the Kaplan-Meier method.

  4. EGFR expression status [ Time Frame: Baseline ]
    Relationship to 3-month PFS will be determined.

  5. HER2 expression status [ Time Frame: Baseline ]
    Relationship to 3-month PFS will be determined.

Other Outcome Measures:
  1. Presence of tumor micro ribonucleic acids (RNAs) like miR-200 [ Time Frame: Baseline ]
    Relationship to 3-month PFS will be determined.

  2. Epithelial to mesenchymal transition states [ Time Frame: Up to 3 years ]
  3. Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 28 days after last administration of trial drugs ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 up to one line of prior systemic chemotherapy for recurrent/metastatic disease; if a platinum-based regimen was received both in the peri-operative setting and again in the metastatic setting, this will be considered 1 line of chemotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 8.5g/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 CD4+ =< 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02122172

Layout table for location information
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Bradley Carthon, MD       winshipcto@emory.edu   
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Peter H. O'Donnell    773-702-7564    podonnel@medicine.bsd.uchicago.edu   
Principal Investigator: Peter H. O'Donnell         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    JLWADE3@sbcglobal.net   
Principal Investigator: James L. Wade         
NorthShore University Health System Completed
Evanston, Illinois, United States, 60201
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Kaitlyn Francese    917-825-5820    Kaitlyn.Francese@nyulangone.org   
Principal Investigator: Arjun Balar, MD         
United States, North Carolina
University of North Carolina - Lineberger Comprehensive Cancer Center Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Anly Thomas    919-962-8591    anly.thomas@email.unc.edu   
Principal Investigator: Matthew Mitowsky, MD         
Sponsors and Collaborators
University of Chicago
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Peter O'Donnell University of Chicago
Layout table for additonal information
Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02122172    
Other Study ID Numbers: 13-0540
NCI-2014-00859 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
13-0540/ 1200.171 ( Other Identifier: University of Chicago )
P30CA014599 ( U.S. NIH Grant/Contract )
First Posted: April 24, 2014    Key Record Dates
Last Update Posted: September 28, 2021
Last Verified: September 2021
Additional relevant MeSH terms:
Layout table for MeSH terms
Urinary Bladder Neoplasms
Urethral Neoplasms
Ureteral Neoplasms
Disease Attributes
Pathologic Processes
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Urethral Diseases
Ureteral Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action