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

NCT ID: NCT03497702

Last Updated: 2018-04-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-08
• Study Completion Date: 2024-01-31

Brief Summary

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.

Conditions

Breast Cancer; Invasive Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Patients 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

Group Type: EXPERIMENTAL

Doxorubicin

Intervention Type: DRUG

60mg/m2 IV every 3 weeks for 4 cycles

Cyclophosphamide

Intervention Type: DRUG

600mg/m2 IV every 3 weeks for 4 cycles

Docetaxel

Intervention Type: DRUG

75mg/m2 IV every 3 weeks for 4 cycles

Letrozole

Intervention Type: DRUG

2.5 mg once daily preoperably

leuprorelin

Intervention Type: DRUG

3.75 mg SC every 4 weeks for premenopausal patients

Interventions

Doxorubicin

60mg/m2 IV every 3 weeks for 4 cycles

Intervention Type: DRUG

Cyclophosphamide

600mg/m2 IV every 3 weeks for 4 cycles

Intervention Type: DRUG

Docetaxel

75mg/m2 IV every 3 weeks for 4 cycles

Intervention Type: DRUG

Letrozole

2.5 mg once daily preoperably

Intervention Type: DRUG

leuprorelin

3.75 mg SC every 4 weeks for premenopausal patients

Intervention Type: DRUG

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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Center, Korea

OTHER_GOV

Sponsor Role: lead

Responsible Party

Keun Seok Lee

Head, Center for Breast Cancer

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Keun Seok Lee, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center

Locations

National Cancer Center

Goyang-si, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Keun Seok Lee, MD, PhD

Role: CONTACT

kslee@ncc.re.kr

+82-31-920-1220

Facility Contacts

Keun Seok Lee, MD, PhD

Role: primary

Other Identifiers

NCC2017-0110

Identifier Type: -

Identifier Source: org_study_id