Clinical trial NCT01622361: Premenopausal Patient With Hormone Responsive, HER2 Negative, Lymph Node Positive Breast Cancer
Official title: A Phase III, Open-Label, Prospective, Randomized, Multicenter, Neo-adjuvant Study of Chemotherapy Versus Endocrine Therapy in Premenopausal Patient With Hormone Responsive, HER2 Negative, Lymph Node Positive Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Neoadjuvant
endocrine therapy
premenopausal
hormone responsive
HER2 negative
lymph node positive
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Korean Breast Cancer Study Group
First posted: 2012-06-19
Enrollment: 290
Sex: FEMALE
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare neo-adjuvant therapy of cytotoxic chemotherapy versus GnRHa with tamoxifen , of response rate(RR) in patients of hormone responsive and HER2 negative, lymph node positive, primary breast cancer in premenopausal women.

Detailed description: 1. Primary objective

   : Response Rate-MRI and/or Caliper
2. Secondary objectives

   * Pathologic complete response
   * Rate of conservation surgery
   * Ki-67 changes and its relationship to treatment response
   * Length of time to maximum response within the treatment period
   * Tolerability of two treatments
   * Disease-free survival(DFS)
   * Overall survival

Eligibility criteria: Inclusion Criteria:

1. Histologically proven primary invasive breast cancer which is thought to be suitable for neo-adjuvant treatment
2. Pathologically proven lymph node positive tumor(FNAB or Core biopsy)
3. Tumor must be ER positive(eligible patients include Allred score 5 and more, Modified Allred 4 and more) and HER-2 negative(IHC score is 0-1+; If IHC score is 2+, the result of FISH or SISH is negative)
4. Premenopausal women

   Premenopausal status as defined by :
   * Last menses within 6 month of randomization or
   * For patients who have had a unilateral oophorectomy, E2 ≥ 20PG/mL and FSH \< 30mIU/Ml within 4 weeks of randomization
5. over 20 years old
6. Pre-treatment haematology and biochemistry values within acceptable limits :

   * ANC ≥ 1.5 × 109/l
   * Hb \> 9g/dl
   * Platelets ≥ 100 × 109/l
   * AST/ALT ≤ 1.5 × ULN(Upper Limit of Normal)
   * ALP ≤ 1.5 × ULN
   * Serum bilirubin ≤ 1.5 × ULN
   * Serum creatinine ≤ 1.5 × ULN
7. ECOG PS of 0 or 1
8. No concomitant medical, psychiatric or geographic problems that might prevent completion of treatment or follow-up
9. Before any study-specific procedures, the appropriate written informed consent must be obtained

Exclusion Criteria:

1. Inflammatory breast cancer
2. Inoperable disease that is judged very unlikely to be rendered operable by neo-adjuvant treatment
3. Known severe hypersensitivity to GnRHa treatment
4. Bilateral invasive breast cancer
5. Other serious illness or medical condition:

   * congestive heart failure or unstable angina pectoris, previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrhythmias
   * history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
   * active uncontrolled infection
6. HRT within 4 weeks of starting treatment
7. Definite contra-indications for the use of corticosteroids.
8. Last 10 years with a history of other malignant tumor (except in the case of basal cell carcinoma or cervical carcinoma in situ, and where treatment consisted solely of resection)
9. Systemic metastatic (Tests for the diagnosis of systemic metastatic comply with the guideline in each institution)
10. Pregnant or breastfeeding women
11. Chronic oral treatment with corticosteroids unless initiated \> 6 months prior to study entry and at low dose (≤ 20 mg methylprednisolone or equivalent).

Primary outcomes:
measure: Response Rate
timeFrame: 6 months
Secondary outcomes:
measure: Pathologic complete response
timeFrame: 6 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
state: Songpa-gu
Study officials:
References:
citation: Gwark S, Noh WC, Ahn SH, Lee ES, Jung Y, Kim LS, Han W, Nam SJ, Gong G, Kim SO, Kim HJ. Axillary Lymph Node Dissection Rates and Prognosis From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer. Front Oncol. 2021 Sep 30;11:741120. doi: 10.3389/fonc.2021.741120. eCollection 2021.
citation: Gwark S, Ahn SH, Noh WC, Lee ES, Jung Y, Kim LS, Han W, Nam SJ, Gong G, Kim SO, Kim HJ. Patient-Reported Outcomes From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer. Front Oncol. 2021 Jul 2;11:608207. doi: 10.3389/fonc.2021.608207. eCollection 2021.
citation: Kim HJ, Noh WC, Lee ES, Jung YS, Kim LS, Han W, Nam SJ, Gong G-, Kim HJ, Ahn SH. Efficacy of neoadjuvant endocrine therapy compared with neoadjuvant chemotherapy in pre-menopausal patients with oestrogen receptor-positive and HER2-negative, lymph node-positive breast cancer. Breast Cancer Res. 2020 May 27;22(1):54. doi: 10.1186/s13058-020-01288-5.