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

Breast Cancer Clinical Trial

— NeoChAI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03497702
• Other study ID #: NCC2017-0110
• Status: Recruiting
• Phase: Phase 2
• First received: March 18, 2018
• Last updated: April 12, 2018
• Start date: May 8, 2017
• Est. completion date: January 2024

Study information

• Verified date: April 2018
• Source: National Cancer Center, Korea
• Contact: Keun Seok Lee, MD, PhD
• Phone: +82-31-920-1220
• Email: kslee[@]ncc.re.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 114
• Est. completion date: January 2024
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 19 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Invasive Breast Cancer

Intervention

Drug:
• Doxorubicin
60mg/m2 IV every 3 weeks for 4 cycles
• Cyclophosphamide
600mg/m2 IV every 3 weeks for 4 cycles
• Docetaxel
75mg/m2 IV every 3 weeks for 4 cycles
• Letrozole
2.5 mg once daily preoperably
• leuprorelin
3.75 mg SC every 4 weeks for premenopausal patients

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Center, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pathologic complete remission (pCR)	pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition])	within 6 weeks following the last dose of chemotherapy
Secondary	Adverse events	Frequency and severity of hematological and non-hematological adverse events and laboratory abnormalities according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0	during 6 months of neoadjuvant chemotherapy
Secondary	Response rate	Overall objective clinical response rate = CR + PR rate, measured by MRI (or US) and assessed by RECIST criteria.	during 6 months of neoadjuvant chemotherapy
Secondary	Downstaging to breast conserving surgery (BCS)	Ratio of the number of patients with breast conserving surgery converted from planned mastectomy over the number of patients with initially planned mastectomy	within 6 weeks following the last dose of chemotherapy
Secondary	Disease free survival	Disease-free survival (DFS) following operation.	Patients will be followed up to 6 years