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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

Tracking Information
First Submitted Date  ICMJE July 2, 2015
First Posted Date  ICMJE July 7, 2015
Last Update Posted Date November 11, 2019
Study Start Date  ICMJE June 2015
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 6, 2015)
Progression free survival [ Time Frame: 4 Years ]
Progression free survival for at least 6 months after initiating therapy
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02491099 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 6, 2015)
The safety profile of Afatinib in USPC patients by CTCAE v4.0 [ Time Frame: 4 Years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE A Phase II Evaluation of Afatinibin Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2/Neu+ Uterine Serous Carcinoma
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Afatinib
Afatinib 40 mgs., Q 21 Day times 4 Cycles
Intervention: Drug: Afatinib
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 6, 2015)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2028
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alessandro D. Santin, M.D. 203-737-4450
Contact: Lisa Baker, R.N. 203-785-6398
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02491099
Other Study ID Numbers  ICMJE 1503015437
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yale University
Study Sponsor  ICMJE Yale University
Collaborators  ICMJE Boehringer Ingelheim
Investigators  ICMJE
Principal Investigator: Alessandro Santin, M.D. Yale University
PRS Account Yale University
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP