Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer (NeoChAI)
Primary Purpose
Breast Cancer, Invasive Breast Cancer
Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Doxorubicin
Cyclophosphamide
Docetaxel
Letrozole
leuprorelin
Sponsored by
About this trial
This is an interventional treatment trial for Breast Cancer
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
Sites / Locations
- National Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Experimental
Arm Description
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
Outcomes
Primary Outcome Measures
pathologic complete remission (pCR)
pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition])
Secondary Outcome Measures
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
Response rate
Overall objective clinical response rate = CR + PR rate, measured by MRI (or US) and assessed by RECIST criteria.
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
Disease free survival
Disease-free survival (DFS) following operation.
Full Information
NCT ID
NCT03497702
First Posted
March 18, 2018
Last Updated
April 12, 2018
Sponsor
National Cancer Center, Korea
1. Study Identification
Unique Protocol Identification Number
NCT03497702
Brief Title
Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
Acronym
NeoChAI
Official Title
Phase II Study of Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2018
Overall Recruitment Status
Recruiting
Study Start Date
May 8, 2017 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Center, Korea
4. Oversight
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
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer, Invasive Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
114 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
60mg/m2 IV every 3 weeks for 4 cycles
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
600mg/m2 IV every 3 weeks for 4 cycles
Intervention Type
Drug
Intervention Name(s)
Docetaxel
Intervention Description
75mg/m2 IV every 3 weeks for 4 cycles
Intervention Type
Drug
Intervention Name(s)
Letrozole
Intervention Description
2.5 mg once daily preoperably
Intervention Type
Drug
Intervention Name(s)
leuprorelin
Intervention Description
3.75 mg SC every 4 weeks for premenopausal patients
Primary Outcome Measure Information:
Title
pathologic complete remission (pCR)
Description
pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition])
Time Frame
within 6 weeks following the last dose of chemotherapy
Secondary Outcome Measure Information:
Title
Adverse events
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
Time Frame
during 6 months of neoadjuvant chemotherapy
Title
Response rate
Description
Overall objective clinical response rate = CR + PR rate, measured by MRI (or US) and assessed by RECIST criteria.
Time Frame
during 6 months of neoadjuvant chemotherapy
Title
Downstaging to breast conserving surgery (BCS)
Description
Ratio of the number of patients with breast conserving surgery converted from planned mastectomy over the number of patients with initially planned mastectomy
Time Frame
within 6 weeks following the last dose of chemotherapy
Title
Disease free survival
Description
Disease-free survival (DFS) following operation.
Time Frame
Patients will be followed up to 6 years
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Keun Seok Lee, MD, PhD
Phone
+82-31-920-1220
Email
kslee@ncc.re.kr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keun Seok Lee, MD, PhD
Organizational Affiliation
National Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Center
City
Goyang-si
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Keun Seok Lee, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
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