Afatinib in Advanced Refractory Urothelial Cancer

The University of Chicago

Status and phase

Terminated

Phase 2

Conditions

Stage III Bladder Cancer

Proximal Urethral Cancer

Stage III Urethral Cancer

Ureter Cancer

Recurrent Bladder Cancer

Stage IV Urethral Cancer

Stage IV Bladder Cancer

Distal Urethral Cancer

Recurrent Urethral Cancer

Treatments

Drug: afatinib dimaleate

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT02122172

IRB13-0540

13-0540

P30CA014599 (U.S. NIH Grant/Contract)

NCI-2014-00859 (Registry Identifier)

13-0540/ 1200.171 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

32 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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