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

Status: Active

Description

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

Arizona

Tucson
Banner University Medical Center - Tucson
Status: Active
Contact: Elizabeth Jennie Collins
Phone: 520-694-9067
Email: jenniecollins@email.arizona.edu

Connecticut

New Haven
Yale University
Status: Active
Contact: Alessandro D. Santin
Phone: 203-737-4450
Email: alessandro.santin@yale.edu

Massachusetts

Boston
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Whitfield Board Growdon
Phone: 617-724-4800
Email: wgrowdon@partners.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

TERTIARY OBJECTIVES:

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.

OUTLINE:

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

Treatment

Lead Organization

Lead Organization
Yale University

Principal Investigator
Alessandro D. Santin

Trial IDs

Primary ID 1503015437
Secondary IDs NCI-2017-00360
Clinicaltrials.gov ID NCT02491099