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.
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.
Overal Status | Start Date | Phase | Study Type |
---|---|---|---|
Recruiting | October 30, 2013 | Phase 2 | Interventional |
Primary Outcome 1 - Measure: Progression-free survival (PFS)
Primary Outcome 1 - Time Frame: 3 months
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
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Gender: All
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Peter O'Donnell
Role: Principal Investigator
Affiliation: University of Chicago
Facility | Status | Contact |
---|---|---|
University of Chicago Chicago, Illinois 60637 United States |
Recruiting |
Peter H. O'Donnell 773-702-7564 podonnel@medicine.bsd.uchicago.edu |
Decatur Memorial Hospital Decatur, Illinois 62526 United States |
Recruiting |
James L. Wade 217-876-6600 JLWADE3@sbcglobal.net |
NorthShore University Health System Evanston, Illinois 60201 United States |
Completed | |
NYU Langone Health New York, New York 10016 United States |
Recruiting |
Kaitlyn Francese 917-825-5820 Kaitlyn.Francese@nyulangone.org |
University of North Carolina - Lineberger Comprehensive Cancer Center Chapel Hill, North Carolina 27599 United States |
Recruiting |
Anly Thomas 919-962-8591 anly.thomas@email.unc.edu |