Clinical Trials /

Afatinib in Advanced Refractory Urothelial Cancer

NCT02122172

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Afatinib in Advanced Refractory Urothelial Cancer
  • Official Title: Afatinib Dimaleate in Treating Patients With Advanced Refractory Urothelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: 13-0540
  • SECONDARY ID: NCI-2014-00859
  • SECONDARY ID: IRB13-0540
  • SECONDARY ID: 13-0540/ 1200.171
  • SECONDARY ID: P30CA014599
  • NCT ID: NCT02122172

Conditions

  • 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

Interventions

DrugSynonymsArms
afatinib dimaleateafatinib, BIBW 2992 MA2, GilotrifTreatment (afatinib)

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (afatinib)ExperimentalPatients receive afatinib dimaleate PO QD on days 1-42. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.
  • afatinib dimaleate

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:3 months
Safety Issue:
Description:Estimated using the Kaplan-Meier method.

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Chicago

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