Clinical Trials /

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

NCT02491099

Description:

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.

Related Conditions:
  • Endometrial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase II Evaluation of Afatinibin Patients With Persistent or Recurrent HER2-positive Uterine Serous Carcinoma
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 1503015437
  • NCT ID: NCT02491099

Conditions

  • HER2/Neu+ Uterine Serous Carcinoma

Interventions

DrugSynonymsArms
AfatinibIrreversible Human Epidermal Growth FactorAfatinib

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
AfatinibExperimentalAfatinib 40 mgs., Q 21 Day times 4 Cycles
  • Afatinib

Eligibility Criteria

        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.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression free survival
Time Frame:4 Years
Safety Issue:
Description:Progression free survival for at least 6 months after initiating therapy

Secondary Outcome Measures

Measure:The safety profile of Afatinib in USPC patients by CTCAE v4.0
Time Frame:4 Years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yale University

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