Clinical Trials /

Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer

NCT02725541

Description:

This is an open label, neoadjuvant phase II study to evaluate the objective response, toxicity, and safety of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Trastuzumab emtansine at a dose of 3.6 mg/kg will be intravenously administered every 3 weeks for a total of 6 weeks. Patients who achieve a partial or complete response after the 6-week treatment (responders) will continue on trastuzumab emtansine for an additional 12 weeks.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer
  • Official Title: Trial of Neoadjuvant Trastuzumab Emtansine in Patients With HER2-Equivocal Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: Pro00013875
  • NCT ID: NCT02725541

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
Trastuzumab emtansineado-trastuzumab emtansine; T-DM1; KADCYCLAExperimental

Purpose

This is an open label, neoadjuvant phase II study to evaluate the objective response, toxicity, and safety of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast cancer. Trastuzumab emtansine at a dose of 3.6 mg/kg will be intravenously administered every 3 weeks for a total of 6 weeks. Patients who achieve a partial or complete response after the 6-week treatment (responders) will continue on trastuzumab emtansine for an additional 12 weeks.

Detailed Description

      NATURE is an open label, neoadjuvant, phase II study designed to evaluate the objective
      response rate of trastuzumab emtansine in patients with newly diagnosed HER2-equivocal breast
      cancer. Patients will receive trastuzumab emtansine at a dose of 3.6 mg/kg via intravenous
      infusion every 3 weeks for a total of 6 weeks (2 21-day cycles). Patients who achieve partial
      or complete response (responders) after the 6-week treatment will continue on trastuzumab
      emtansine for an additional 12 weeks (4 cycles). The primary objective will be objective
      response rate after 6 weeks of neoadjuvant trastuzumab emtansine. Secondary objectives will
      include imaging response (ultrasound and magnetic resonance imaging) after six weeks of
      neoadjuvant trastuzumab emtansine and toxicity and efficacy of trastuzumab emtansine. After
      completion of continued trastuzumab emtansine treatment, pathological complete response rate
      of responders as a whole and according to estrogen receptor status will be explored. Markers
      related to the mechanism of action of trastuzumab emtansine (HER2 copy number in circulating
      tumor cells; tissue expression of PTEN, PI3K, and other potential candidate markers) will
      also be explored.
    

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalTrastuzumab emtansine at a dose of 3.6 mg/kg will be administered via intravenous infusion for 6 weeks (two 21-day cycles).
  • Trastuzumab emtansine

Eligibility Criteria

        Inclusion Criteria:

          -  Female gender;

          -  Age ≥18 years;

          -  Eastern Cooperative Oncology Group performance status of 0-1;

          -  Histologically confirmed invasive breast cancer;

          -  Primary tumor greater than or equal to 1 cm diameter, as measured by clinical
             examination and mammography or ultrasound;

          -  Any N;

          -  No evidence of metastasis (M0) (isolated supra-clavicular node involvement allowed);

          -  HER2 low or equivocal status in the invasive component of the primary tumor (confirmed
             by a central certified laboratory prior to study entry)

               -  HER2 low expression: 1+/2+ by immunohistochemistry and/or HER2/CEP17 ratio <2.0
                  with HER2 copy number <6.0 signals/cell

               -  HER2 equivocal expression: HER2 copy number ≥4.0 and <6.0 signals/cell;

          -  Hematopoietic status:

        Absolute neutrophil count ≥ 1.0 x 10^9/L, Platelet count ≥ 100 x 10^9/L, Hemoglobin at
        least 9 g/dL;

        • Hepatic status: Serum total bilirubin ≤1 x upper limit of normal (ULN; In the case of
        known Gilbert's syndrome, a higher serum total bilirubin [< 1.5 x ULN] is allowed),
        Aspartate aminotransferase and alanine aminotransferase ≤1.5 x ULN, Alkaline phosphatase ≤
        1.5 x ULN;

        • Renal status: Creatinine ≤1.5 mg/dL;

          -  International Normalized Ratio ≤1.5 x ULN;

          -  Baseline left ventricular ejection fraction ≥50%, as measured by echocardiography or
             multigated acquisition scan;

          -  Negative serum or urine β-human chorionic gonadotropin pregnancy test within 7 days
             prior study entry for patients of childbearing potential. Women of childbearing
             potential must use effective contraception (barrier method [condoms, diaphragm] in
             conjunction with spermicidal jelly, or total abstinence. Oral, injectable, and
             implantable hormonal contraceptives are not allowed) for the duration of the study and
             for at least 7 months after the last dose of study treatment;

          -  Signed informed consent form (ICF);

          -  Patient accepts to make available tumor samples for submission to central laboratory
             to conduct translational studies as part of this protocol.

        Exclusion Criteria:

          -  Previous (less than 5 years) or current history of malignant neoplasms, except for
             curatively treated basal and squamous cell carcinoma of the skin and carcinoma in situ
             of the cervix;

          -  Patients with a prior malignancy diagnosed more than 5 years prior to study entry;

          -  Preexisting peripheral neuropathy ≥ grade 2;

          -  Known history of uncontrolled or symptomatic angina, clinically significant
             arrhythmias, congestive heart failure, transmural myocardial infarction, uncontrolled
             hypertension (≥180/110), unstable diabetes mellitus, dyspnea at rest, or chronic
             oxygen therapy;

          -  Concurrent disease or condition that would make the patient inappropriate for study
             participation or any serious medical disorder that would interfere with the patient's
             safety;

          -  Unresolved or unstable serious adverse events from prior administration of another
             investigational drug;

          -  Dementia, altered mental status, or any psychiatric condition that would prevent the
             understanding or rendering of ICF;

          -  Concurrent neoadjuvant cancer therapy (chemotherapy, radiation therapy, immunotherapy,
             or biologic therapy other than the trial therapy);

          -  Concurrent treatment with an investigational agent or participation in another
             therapeutic clinical trial;

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to trastuzumab emtansine or its components;

          -  Ejection fraction <55% or below the lower limit of the institutional normal range;

          -  Pregnant or lactating women;

          -  Concomitant use of cytochrome P450 3A4 inhibitors or inducers;

          -  Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
             active or uncontrolled infection, uncontrolled diabetes) that could cause unacceptable
             safety risks or compromise compliance with the protocol;

          -  Active infection requiring intravenous or oral antibiotics;

          -  Patients unwilling or unable to comply with the protocol.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:6 weeks
Safety Issue:
Description:Determine the objective response rate after 6 weeks of neoadjuvant trastuzumab emtansine (RECIST 1.1)

Secondary Outcome Measures

Measure:Radiological response
Time Frame:6 weeks
Safety Issue:
Description:Determine radiological response after 6 weeks of neoadjuvant trastuzumab emtansine
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:18 weeks
Safety Issue:
Description:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Jenny C. Chang, MD

Trial Keywords

  • HER2 equivocal
  • Trastuzumab emtansine
  • Breast cancer

Last Updated

September 12, 2016