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Afatinib in Advanced Refractory Urothelial Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Chicago
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT02122172
First received: April 22, 2014
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • Overall response rate (CR + PR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Median progression-free survival (PFS ) time [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • Overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.

  • EGFR expression status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Relationship to 3-month PFS will be determined.

  • HER2 expression status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Relationship to 3-month PFS will be determined.


Other Outcome Measures:
  • Presence of tumor micro ribonucleic acids (RNAs) like miR-200 [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Relationship to 3-month PFS will be determined.

  • Epithelial to mesenchymal transition states [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Incidence of adverse events, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 28 days after last administration of trial drugs ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 33
Study Start Date: February 2014
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02122172

Locations
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Peter H. O'Donnell    773-702-7564    podonnel@medicine.bsd.uchicago.edu   
Principal Investigator: Peter H. O'Donnell         
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
Contact: James L. Wade    217-876-6600    JLWADE3@sbcglobal.net   
Principal Investigator: James L. Wade         
Kellogg Cancer Center - Evanston Hospital Recruiting
Evanston, Illinois, United States, 60201
Contact: Daniel H. Shevrin    847-570-2515    dshevrin@northshore.org   
Principal Investigator: Daniel H. Shevrin         
Sponsors and Collaborators
University of Chicago
Investigators
Principal Investigator: Peter O'Donnell University of Chicago
  More Information

No publications provided

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02122172     History of Changes
Other Study ID Numbers: 13-0540, NCI-2014-00859, IRB13-0540, 13-0540/ 1200.171, P30CA014599
Study First Received: April 22, 2014
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Urethral Neoplasms
Urinary Bladder Neoplasms
Neoplasms
Neoplasms by Site
Urethral Diseases
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Urologic Neoplasms

ClinicalTrials.gov processed this record on November 25, 2014