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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02491099
Recruitment Status : Recruiting
First Posted : July 7, 2015
Last Update Posted : November 11, 2019
Boehringer Ingelheim
Information provided by (Responsible Party):
Yale University

Brief Summary:
Primary Objective: To assess the activity of Afatinib in patients with persistent or recurrent uterine serous carcinoma overexpressing HER2/neu with the frequency of patients who survive progression-free for at least 6 months after initiating therapy. Secondary Objectives: To assess objective response rate and durable disease control rate. To assess overall survival. To assess the safety profile of Afatinib in uterine serous carcinoma patients.

Condition or disease Intervention/treatment Phase
HER2/Neu+ Uterine Serous Carcinoma Drug: Afatinib Phase 2

Detailed Description:
Exploratory/correlative objectives: To systematically evaluate HER2/neu expression/amplification using standardized scoring criteria for both breast and gastric cancer and correlate clinical response in uterine serous carcinoma patients with HER2/neu scoring results. To correlate objective response rate, PFS and overall survival with the presence/absence of phosphatidyl inositol 3-kinase catalytic subunit and F-box/WD repeat-containing protein mutations by standard Sanger sequencing, and presence/absence of Cyclin E2 overexpression by IHC in endometrial cancer patients overexpressing HER2/neu treated with Afatinib. To study HER2/neu extracellular domain circulating levels in the plasma of uterine serous carcinoma patients overexpressing HER2/neu before and during Afatinib treatment to elucidate whether changes in HER2/neu extracellular domain would predict response to Afatinib and to determine peripheral blood natural killer cell numbers and activity in HER2/neu+ uterine serous carcinoma patients before and during Afatinib treatment to assess the possible therapeutic contributions of immune mechanisms of action of Afatinib.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Afatanib, an Irreversible Human Epidermal Growth Factor Receptor 2 (Her2/Neu) Tyrosine Kinase Inhibitor, in Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma
Study Start Date : June 2015
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2028

Arm Intervention/treatment
Experimental: Afatinib
Afatinib 40 mgs., Q 21 Day times 4 Cycles
Drug: Afatinib
Afatinib, 40 mg orally once daily on a 21 day cycle for the first 12 weeks, then every 28 days for subsequent cycles until progression
Other Name: Irreversible Human Epidermal Growth Factor

Primary Outcome Measures :
  1. Progression free survival [ Time Frame: 4 Years ]
    Progression free survival for at least 6 months after initiating therapy

Secondary Outcome Measures :
  1. The safety profile of Afatinib in USPC patients by CTCAE v4.0 [ Time Frame: 4 Years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have persistent or recurrent histologically confirmed uterine serous carcinoma, harbor a tumor HER2/neu+ based upon IHC staining score of 3+ or 2+ with confirmed gene amplification by FISH.
  • Have measurable disease.
  • Have at least one target lesion to be used to assess response as defined by RECIST v1.1.
  • After undergoing surgery may be optimally or sub optimally debulked, with measurable recurrent 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, granulocytes greater than or equal to 1500/ul., creatinine less than or equal to 2.0 mg/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. Should be free of significant infection.
  • Patients with recurrent disease may have received multiple prior chemotherapies for treatment of their uterine cancer.
  • May have received prior trastuzumab therapy alone or in combination with chemotherapy with 2 week washout period required between trastuzumab treatment and first 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 of contraception.
  • Must be 18 years of age.

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.
  • Patients who have a significant history of cardiac disease, uncontrolled hypertension, unstable angina, uncontrolled congestive heart failure, or uncontrolled arrhythmias within 6 months of registration. Patients with any unstable medical issue, active treatment for symptomatic pulmonary embolism, CVA, renal or hepatic insufficiency, active infection/sepsis requiring 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 HIV and active hepatitis, even if liver function studies are in the eligible range. Known hemorrhagic diathesis or active bleeding disorder.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02491099

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Contact: Alessandro D. Santin, M.D. 203-737-4450
Contact: Lisa Baker, R.N. 203-785-6398

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United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Setsuko Chambers, M.D.    520-626-0950   
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Alessandro D. Santin, M.D.    203-737-4450   
Contact: Lisa Baker, R.N.    203-785-6398   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Whitfield Growdon, MD    617-724-4800   
Contact: Louisa Bauer, RN    617-643-5415   
Principal Investigator: Whitfield Growdon, MD         
Sponsors and Collaborators
Yale University
Boehringer Ingelheim
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Principal Investigator: Alessandro Santin, M.D. Yale University

Publications of Results:

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Responsible Party: Yale University Identifier: NCT02491099     History of Changes
Other Study ID Numbers: 1503015437
First Posted: July 7, 2015    Key Record Dates
Last Update Posted: November 11, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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Cystadenocarcinoma, Serous
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Cystic, Mucinous, and Serous
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors