Afatinib Dimaleate in Treating Patients with Locally Advanced or Metastatic Penile Cancer That Cannot Be Removed by Surgery

Inclusion Criteria

• Histologically or cytologically confirmed PSCC
• Patients with metastatic (lymph node or distant metastasis, i.e. N+ or M1) or locally advanced unresectable PSCC
• Progressive disease after >= 1 prior chemotherapy regimens
• Measurable disease by RECIST 1.1 criteria
• Prior regimen within 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) > 1500/mm^3
• Platelet count > 100,000/mm^3
• Estimated creatinine clearance >= 45 ml/min
• Total bilirubin < 1.5 times upper limit of institutional normal
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 times the upper limit of institutional normal (ULN)
• Hemoglobin >= 8.5 g/dl
• Resolution of all acute toxic effects of prior chemotherapy or surgical procedures to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade < 1, in the opinion of the treating physician
• Ability to understand and willingness to sign a written informed consent that is consistent with International Council for Harmonisation to organize applications to regulatory authorities for registration of pharmaceuticals for human use-good clinical practice (ICH-GCP) guidelines
• Age >= 18 years or age of majority at the participating site, whichever is greater
• Availability of 20 archival formalin-fixed paraffin embedded (FFPE) tumor tissue slides (15 of 10 uM thick sections, and 5 of 5 uM thick sections)

Exclusion Criteria

• Patients will have recovered from toxicities from prior systemic anticancer treatment or local therapies
• Prior EGFR inhibitors
• Major surgery within 4 weeks or minor surgery within 2 weeks before registration or scheduled for surgery during the projected course of the study; wounds will be completely healed prior to study entry and patients recovered from all toxicities from surgery; placement of vascular access device is not considered major or minor surgery in this regard
• Prior radiation therapy is allowed as long as the irradiated area was not the sole source of measurable disease and radiotherapy was completed with recovery from toxicity, at least 3 weeks prior to enrollment; if the irradiated area is the only site of disease, there will be progressive disease
• History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, congestive heart failure New York Heart Association (NYHA) classification of 3, unstable angina or poorly controlled arrhythmia as determined by the investigator; myocardial infarction within 6 months prior to registration
• Any history of or concomitant condition that, in the opinion of the investigator, would compromise the patient’s ability to comply with the study or interfere with the evaluation of the efficacy and safety of the test drug
• Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured
• Requiring treatment with any of the prohibited concomitant medications that cannot be stopped for the duration of trial participation
• Known pre-existing interstitial lung disease
• Any history or presence of poorly controlled gastrointestinal disorders that could affect the absorption of the study drug (e.g. Crohn’s disease, ulcerative colitis, chronic diarrhea, malabsorption)
• Active hepatitis B infection (defined as presence of hepatitis [hep] B surface antigen [sAg] and/ or hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as presence of hep C ribonucleic acid [RNA]) and/or known human immunodeficiency virus (HIV) carrier
• Meningeal carcinomatosis
• Patients with active brain or subdural metastases are not eligible, unless they have completed local (radiation) therapy and have discontinued the use of corticosteroids or have been on stable dose of corticosteroids for at least 4 weeks before starting study treatment; any symptoms attributed to brain metastases will be stable for at least 4 weeks before starting study treatment
• Any active or uncontrolled infection