Afatinib in Advanced Refractory Urothelial Cancer

Sponsor

University of Chicago (Other)

Overall Status

Recruiting

CT.gov ID

NCT02122172

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

115.4

Anticipated Duration (Months)

15.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Drug: afatinib dimaleate Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

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:

To determine the overall response rate (complete response [CR] + partial response [PR]), median progression free survival, and overall survival for the same treated population.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

95 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer

Actual Study Start Date :

Oct 30, 2013

Anticipated Primary Completion Date :

Jun 12, 2022

Anticipated Study Completion Date :

Jun 12, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: afatinib dimaleate Given PO Other Names: afatinib BIBW 2992 MA2 Gilotrif Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: 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.

Drug: afatinib dimaleate

Given PO

Other Names:

afatinib

BIBW 2992 MA2

Gilotrif

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS) [3 months]
Estimated using the Kaplan-Meier method.

Secondary Outcome Measures

Overall response rate (CR + PR) [Up to 3 years]
Median progression-free survival (PFS ) time [Up to 3 years]
Estimated using the Kaplan-Meier method.
Overall survival [Up to 3 years]
Estimated using the Kaplan-Meier method.
EGFR expression status [Baseline]
Relationship to 3-month PFS will be determined.
HER2 expression status [Baseline]
Relationship to 3-month PFS will be determined.

Other Outcome Measures

Presence of tumor micro ribonucleic acids (RNAs) like miR-200 [Baseline]
Relationship to 3-month PFS will be determined.
Epithelial to mesenchymal transition states [Up to 3 years]
Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [Up to 28 days after last administration of trial drugs]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322
2	University of Chicago	Chicago	Illinois	United States	60637
3	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
4	NorthShore University Health System	Evanston	Illinois	United States	60201
5	NYU Langone Health	New York	New York	United States	10016
6	University of North Carolina - Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599