Patient case: 49-year-old female with lung cancer; genetic feature: ERBB2

Clinical trial: Afatinib in Advanced Refractory Urothelial Cancer

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.

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: 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

Relevance to patient case: not relevant