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

Status: Active


This phase II trial studies how well afatinib works in treating patients with stage I-IV HER2 positive uterine cancer that has come back after a period of improvement. Afatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Eligibility Criteria

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
  • Granulocytes 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

Exclusion Criteria

  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancers are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • 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

Locations & Contacts


Banner University Medical Center - Tucson
Status: Active
Contact: Elizabeth Jennie Collins
Phone: 520-694-9067


New Haven
Yale University
Status: Active
Contact: Alessandro D. Santin
Phone: 203-737-4450


Massachusetts General Hospital Cancer Center
Status: Active
Contact: Whitfield Board Growdon
Phone: 617-724-4800

Trial Objectives and Outline


I. To assess the activity of afatinib in patients with persistent or recurrent uterine serous carcinoma (USC) overexpressing HER2/neu with the frequency of patients who respond to afatinib by either attaining partial or complete response or by surviving progression-free for at least 6 months after initiating therapy.


I. To assess objective response rate (ORR) and durable disease control rate (DDCR).

II. To assess overall survival (OS).

III. To assess the safety profile of afatinib in USC patients.


I. To systematically evaluate HER2/neu expression/amplification using standardized scoring criteria for both breast and gastric cancer and correlate clinical response in USC patients with HER2/neu scoring results.

II. To correlate ORR, progression free survival (PFS), and OS with the presence/absence of PIK3CA (phosphatidyl inositol 3-kinase catalytic subunit) and FBXW7 (F-box/WD repeat-containing protein) mutations by standard Sanger sequencing, and presence/absence of cyclin E2 overexpression by immunohistochemistry (IHC) in endometrial cancer patients overexpressing HER2/neu treated with afatinib.

III. To study HER2/neu extracellular domain (ECD) circulating levels in the plasma of USC patients overexpressing HER2/neu before, and during afatinib treatment to elucidate whether changes in HER2/neu ECD would predict response to afatinib.

IV. To determine peripheral blood natural killer (NK) cell numbers and activity in HER2/neu+ USC patients before, and during afatinib treatment to assess the possible therapeutic contributions of immune mechanisms of action of afatinib.


Patients receive afatinib orally (PO) once daily (QD) on days 1-21. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive afatinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, then every 6 months for 3 years, and then annually thereafter.

Trial Phase & Type

Trial Phase

Phase II

Trial Type


Lead Organization

Lead Organization
Yale University

Principal Investigator
Alessandro D. Santin

Trial IDs

Primary ID 1503015437
Secondary IDs NCI-2017-00360 ID NCT02491099