A Phase II Evaluation of Afatinib in Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma

Inclusion Criteria:

• Patients must have persistent or recurrent histologically confirmed uterine serouscarcinoma, harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ withconfirmed gene amplification by FISH.

• Have measurable disease.

• Have at least one target lesion to be used to assess response as defined by RECISTv1.1.

• After undergoing surgery may be optimally or sub optimally debulked, with measurablerecurrent disease of any previous substage.

• Diagnosis histologically confirmed by a gynecologic pathologist as containing >10%uterine papillary serous adenocarcinoma in the specimen.

• Have adequate bone marrow function.

• 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 2.0mg/kl, bilirubin < 1.5 X laboratory normal, SGOT/SGPT <3 X laboratory normal.

• Have an ECOG performance status of 0 or 1.

• Have signed an approved consent.

• Have recovered from effects of recent surgery, radiotherapy or chemotherapy. Shouldbe free of significant infection.

• Patients with recurrent disease may have received multiple prior chemotherapies fortreatment of their uterine cancer.

• May have received prior trastuzumab therapy alone or in combination withchemotherapy with 2 week washout period required between trastuzumab treatment andfirst dose of Afatanib.

• 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 ofcontraception.

• Must be 18 years of age.

• Patients with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment ofthe investigational regimen are eligible for this trial. NOTE: Patients with prioranthracycline exposure are NOT eligible.

Exclusion Criteria:

• Patients who have a significant history of cardiac disease, uncontrolledhypertension, unstable angina, uncontrolled congestive heart failure, oruncontrolled arrhythmias within 6 months of registration. Patients with any unstablemedical issue, active treatment for symptomatic pulmonary embolism, CVA, renal orhepatic insufficiency, active infection/sepsis requiring IV antibiotics, knownbrain/leptomengial involvement of the disease, active neurological disease,dementia.

• Patients who have received prior therapy with any irreversible human epidermalgrowth factor receptor tyrosine kinase inhibitor.

• Patients who have an uncontrolled seizure disorder or active neurological disease.Patients known to be seropositive for HIV and active hepatitis, even if liverfunction studies are in the eligible range. Known hemorrhagic diathesis or activebleeding disorder.