Afatinib in Advanced Refractory Urothelial Cancer

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.

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