Afatinib in Advanced Refractory Urothelial Cancer

NCT02122172 | Terminated Phase 2 Results DMC FDA Drug

• 5 other identifiers: 13-0540NCI-2014-00859IRB13-054013-0540/ 1200.171P30CA014599
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 6

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) and the sum must also demonstrate an absolute increase of at least 5mm, or unequivocal progression of existing non-target lesions, or the appearance of new lesions. Estimated at 3 months using the Kaplan-Meier method.

  3 months

Secondary Outcomes (5)

• Overall Response Rate

  Up to 3 years

• Median Progression-free Survival (PFS ) Time

  Up to 3 years

• Median Overall Survival (OS) Time

  Up to 3 years

• EGFR Expression Status

  Baseline

• HER2 Expression Status

  Baseline

Other Outcomes (2)

• Presence of Tumor Micro Ribonucleic Acids (RNAs) Like miR-200

  Baseline

• Epithelial to Mesenchymal Transition States

  Up to 3 years

Study Arms (1)

Treatment (afatinib)

EXPERIMENTAL

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; Other: laboratory biomarker analysis

Interventions

afatinib dimaleate DRUG

Given PO

Also known as: afatinib, BIBW 2992 MA2, Gilotrif

Treatment (afatinib)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (afatinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Chicago: lead
• National Cancer Institute (NCI): collaborator

Study Sites (6)

Emory University Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Decatur Memorial Hospital

Decatur, Illinois, 62526, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

University of North Carolina - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Urethral Neoplasms; Ureteral Neoplasms

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Urethral Diseases; Ureteral Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Peter O'Donnell
• Organization: University of Chicago

podonnel@bsd.uchicago.edu

(773) 702-7564

Study Officials

• Peter O'Donnell

  University of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 24, 2014
• Study Start: September 13, 2017
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: April 25, 2025
• Results First Posted: April 25, 2025

Record last verified: 2025-04

Locations

US (6)