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

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

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

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Invasive Breast Cancer
• Intervention / Treatment: Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Letrozole; Drug: leuprorelin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 114
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Keun Seok Lee, MD, PhD; Phone Number: +82-31-920-1220; Email: kslee@ncc.re.kr

Study Locations

• Korea, Republic of
  • Goyang-si, Korea, Republic of
    • Recruiting
    • National Cancer Center
    • Contact: Keun Seok Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Doxorubicin; 60mg/m2 IV every 3 weeks for 4 cycles; Drug: Cyclophosphamide; 600mg/m2 IV every 3 weeks for 4 cycles; Drug: Docetaxel; 75mg/m2 IV every 3 weeks for 4 cycles; Drug: Letrozole; 2.5 mg once daily preoperably; Drug: leuprorelin; 3.75 mg SC every 4 weeks for premenopausal patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Disease free survival	Disease-free survival (DFS) following operation.	Patients will be followed up to 6 years

Collaborators and Investigators

• Sponsor: National Cancer Center, Korea
• Investigators: Principal Investigator: Keun Seok Lee, MD, PhD, National Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2017
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): January 1, 2024

Study Registration Dates

• First Submitted: March 18, 2018
• First Submitted That Met QC Criteria: April 12, 2018
• First Posted (Actual): April 13, 2018

Study Record Updates

• Last Update Posted (Actual): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 12, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Docetaxel; Cyclophosphamide; Letrozole; Leuprolide; Doxorubicin
• Other Study ID Numbers: NCC2017-0110

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No