Clinical trial NCT03497702: Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer
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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Breast Cancer
Invasive Breast Cancer
Lead sponsor: National Cancer Center, Korea
Sponsor class: OTHER_GOV
First posted: 2018-04-13
Enrollment: 114
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: pathologic complete remission (pCR)
timeFrame: within 6 weeks following the last dose of chemotherapy
Secondary outcomes:
measure: Adverse events
timeFrame: during 6 months of neoadjuvant chemotherapy
measure: Response rate
timeFrame: during 6 months of neoadjuvant chemotherapy
measure: Downstaging to breast conserving surgery (BCS)
timeFrame: within 6 weeks following the last dose of chemotherapy
measure: Disease free survival
timeFrame: Patients will be followed up to 6 years
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
Study officials:
affiliation: National Cancer Center
name: Keun Seok Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: