Afatinib in Advanced Refractory Urothelial Cancer

NCT ID: NCT02122172

Last Updated: 2025-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-13
• Study Completion Date: 2024-04-04

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.

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

OUTLINE:

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

afatinib dimaleate

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

afatinib dimaleate

Given PO

Intervention Type: DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

afatinib; BIBW 2992 MA2; Gilotrif

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter O'Donnell

Role: PRINCIPAL_INVESTIGATOR

University of Chicago

Locations

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

NorthShore University Health System

Evanston, Illinois, United States

NYU Langone Health

New York, New York, United States

University of North Carolina - Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2014-00859

Identifier Type: REGISTRY

Identifier Source: secondary_id

IRB13-0540

Identifier Type: -

Identifier Source: secondary_id

13-0540/ 1200.171

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA014599

Identifier Type: NIH

Identifier Source: secondary_id

View Link

13-0540

Identifier Type: -

Identifier Source: org_study_id