Clinical Trials /

Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer

NCT03497702

Description:

This is an exploratory interventional study that initiates chemotherapy with letrozole in patients with estrogen receptor positive/HER2-negative breast cancer preoperably.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
  • Official Title: Phase II Study of Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: NCC2017-0110
  • NCT ID: NCT03497702

Conditions

  • Breast Cancer
  • Invasive Breast Cancer

Interventions

DrugSynonymsArms
DoxorubicinExperimental
CyclophosphamideExperimental
DocetaxelExperimental
LetrozoleExperimental
leuprorelinExperimental

Purpose

This is an exploratory interventional study that initiates chemotherapy with letrozole in patients with estrogen receptor positive/HER2-negative breast cancer preoperably.

Detailed Description

      STUDY RATIONALE: Patients with ER+/HER2- operable breast cancers who are candiate of
      neoadjuant chemotherapy generally receive chemotherapy alone before operation, followed by
      adjuvant endocrine therapy. Because endocrine therapy is primarily delivered in the
      postoperative setting, the ability to add the efficacy of aromatase inhibitors combined with
      chemotherapy is lost. This study offers the unique opportunity to assess the synergistic or
      additive responsiveness of breast tumors to endocrine therapy plus chemotherapy while the
      tumors are still in vivo by treating patients with an aromatast inhibitor combined with
      chemotherapy before surgery and assessing pCR rates.

      PRIMARY OBJECTIVE: The primary objective is to determine the frequency of pCR in breast and
      axilla.
    

Trial Arms

NameTypeDescriptionInterventions
ExperimentalExperimentalPatients receive neoadjuvant chemotherapy (doxorubicin 60mg/m2 IV and cyclophosphamide 600mg/m2 IV on day 1 every 3 weeks for 4 cycles followed by docetaxel 75mg/m2 IV on day 1 every 3 weeks for 4 cycles) plus letrozole with or without leuproelin depending on menopausal status
  • Doxorubicin
  • Cyclophosphamide
  • Docetaxel
  • Letrozole
  • leuprorelin

Eligibility Criteria

        Inclusion Criteria:

          -  Pathologically proven breast cancer patients who are candidate of neoadjuvant
             chemotherapy with AC followed by Docetaxel

          -  Age: 19-70 years

          -  ER or PR positive ,cT2-3N0 or cT1-3/N+ M0 (ER-positive ≥1% nuclear staining by
             immunohistochemistry , Allred score≥3 )

          -  Available FFPE tissue for biomarker study

          -  HER2-negative by ASCO/CAP guideline

          -  Patients who agree to adequate contraception

          -  ECOG scores of 0-2

          -  Normal or acceptable kidney, liver, cardiovascular, and bone marrow functions

          -  Patients who provide consent

        Exclusion Criteria:

          -  Inflammatory breast cancer

          -  Distant metastasis

          -  Cerebral vascular accidents including transient ischemic attack

          -  Pulmanary thromboembolism or deep vein thrombosis with 6 months; however, patients who
             received more than 6 weeks of anticoagulation within 6 months and remains asymptomatic
             are eligible.

          -  With a history of malignant tumor or complicated with other malignant tumors in
             addition to breast cancer, except for non-melanoma skin cancer, curatively resected
             early gastric cancer, differentiated thyoid cancer < 1 cm, or other cured malignant
             tumor without recurrence for at least 3 years

          -  Ejection Fraction <55% by MUGA scan / Echo CG

          -  No available tissue for biomarker study

          -  Pregnant or lactating women

          -  Patients with other serious diseases or medical conditions: Pituitary adenoma,
             Malabsorption syndrome, Major resection of gastrointestinal tract, Corrected QT
             interval > 480 msec, Congestive heart failure or unstable angina pectoris, myocardial
             infarction, stent insertion, angioplasty, coronary bypass surgery, symptomatic
             peripheral artery disease within 6 months before the enrollment

          -  NYHA class III or IV congestive heart failure

          -  Uncontrolled hypertension and uncontrolled high-risk arrhythmia considered by the
             investigator

          -  Major surgery, major trauma, and/or unhealed wound, fracture, or ulcer within 4 weeks

          -  Acute hemorrhage or hemorrhagic tendency

          -  Obvious neurological or psychiatric disorders, including psychosis, epileptic dementia
             and other diseases which may affect the understanding and sign of the informed consent

          -  Uncontrolled acute infection

          -  Patients with allergic constitution and any known or suspected drug allergy

          -  Concurrent use of other investigational drugs; or participating in other clinical
             trials involving investigational drugs within 30 days before this study

          -  Patients with mental illness or other conditions affecting the patient compliance

          -  Not suitable for the trial considered by the investigator
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:pathologic complete remission (pCR)
Time Frame:within 6 weeks following the last dose of chemotherapy
Safety Issue:
Description:pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition])

Secondary Outcome Measures

Measure:Adverse events
Time Frame:during 6 months of neoadjuvant chemotherapy
Safety Issue:
Description:Frequency and severity of hematological and non-hematological adverse events and laboratory abnormalities according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0
Measure:Response rate
Time Frame:during 6 months of neoadjuvant chemotherapy
Safety Issue:
Description:Overall objective clinical response rate = CR + PR rate, measured by MRI (or US) and assessed by RECIST criteria.
Measure:Downstaging to breast conserving surgery (BCS)
Time Frame:within 6 weeks following the last dose of chemotherapy
Safety Issue:
Description:Ratio of the number of patients with breast conserving surgery converted from planned mastectomy over the number of patients with initially planned mastectomy
Measure:Disease free survival
Time Frame:Patients will be followed up to 6 years
Safety Issue:
Description:Disease-free survival (DFS) following operation.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Center, Korea

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