Afatinib in Treating Patients with Recurrent Stage I-IV HER2 Positive Uterine Cancer

Inclusion Criteria

• Patients must have persistent or recurrent histologically confirmed USC
• Patients must harbor a tumor HER2/neu+ based upon IHC staining score of “3+” or 2+ with confirmed gene amplification by fluorescence in situ hybridization (FISH) to be included
• All patients must have measurable disease; measurable disease is defined as lesions which can be measured by physical examination or by means of medical imaging techniques; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be >= 20 mm when measured by conventional techniques, including palpation or plain x-ray, or >= 10 mm when measured by spiral computed tomography (CT) and/or magnetic resonance imaging (MRI); ascites and pleural effusions are not to be considered measurable disease
• Patients must have at least one “target lesion” to be used to assess response on this protocol as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1; tumors within a previously irradiated field will be designated as “non-target” lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
• After undergoing surgery, patients may be optimally or sub optimally debulked
• Patients with measurable recurrent disease of any previous substage (I-IV) are eligible to enrollment
• The diagnosis must be histologically confirmed by a gynecologic pathologist as containing >= 10% uterine papillary serous (UPSC) adenocarcinoma in the specimen
• White blood cell (WBC) greater than or equal to 3,000/ul
• Platelets greater than or equal to 75,000/ul
• Neutrophils greater than or equal to 1500/ul
• Creatinine less than or equal to 2.0 mg/dL
• Bilirubin =< 1.5 x laboratory normal
• Serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) =< 3 x laboratory normal
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have signed an approved informed consent
• Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy; they should be free of significant infection
• Patients with recurrent disease may have received multiple prior chemotherapies for treatment of their uterine cancer
• Patients may have received prior trastuzumab therapy alone or in combination with chemotherapy; a 2 week washout period is required between trastuzumab treatment and first dose of afatinib
• Patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to the study entry and be practicing an effective form of contraception
• Patients must be at least 18 years of age. The safety and efficacy of Afatinib in pediatric patients has not been established
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. NOTE: Patients with prior anthracycline exposure are NOT eligible

Exclusion Criteria

• Patients who have a significant history of cardiac disease, i.e., uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias within 6 months of registration (New York Heart Association [NYHA] classification III-IV)
• Patients with any unstable medical issue (including cardiac issues as above, active treatment for symptomatic pulmonary embolism, cerebrovascular accident [CVA], renal or hepatic insufficiency, active infection/sepsis requiring intravenous [IV] antibiotics)
• Known brain/leptomengial involvement of the disease, active neurological disease, dementia
• Patients who have received prior therapy with any irreversible human epidermal growth factor receptor tyrosine kinase inhibitor
• Patients who have an uncontrolled seizure disorder, or active neurological disease
• Patients known to be seropositive for human immunodeficiency virus (HIV) and active hepatitis, even if liver function studies are in the eligible range
• Known hemorrhagic diathesis or active bleeding disorder