Stage I HER2 Positive Invasive Breast Cancer De-escalation Study(IRIS)

Study Overview
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Brief Summary
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This is an open label, phase II study evaluating the efficacy and safety of trastuzumab combined with oral chemotherapy or endocrine therapy in patients with HER-2 positive stage I breast cancer.

Detailed Description
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This study has two cohorts. In Cohort A, patients who met the inclusion criteria(ER，PR<10%, T≤2cm or ER,PR ≥10% 1cm<T≤2cm）would be given capecitabine for 6 cycles with standard trastuzumab for 1 year, in which HR+ patients would be given endocrine therapy for 5 years. In Cohort B, patients who met the inclusion criteria(ER,PR ≥10% T≤1cm) would be given endocrine therapy (premenopausal: tamoxifen or toremifene; postmenopausal: letrozole or anastrozole or exemestane) combined with standard trastuzumab for 1 year and complete endocrine therapy for 5 years.

Official Title
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An Open-label,Phase II Study Evaluating the Efficacy and Safety of Trastuzumab Combined With Oral Chemotherapy or Endocrine Therapy in Patients With HER-2 Positive Stage I Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine and trastuzumab
* Drug: endocrine therapy and trastuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females 18-70 years old; Pathological confirmed of stage I breast cancer: histologically confirmed that the longest diameter of invasive cancer is no more than 2cm and the lymph node is negative (N0); In IRIS-A cohort, if a patient is HR negative(ER/PR<10%), the longest diameter of invasive cancer could not exceed 2cm; while if a patient is HR positive(ER and/or PR ≥10%）,the longest diameter of invasive cancer is greater than 1cm and no more than 2cm; In IRIS-B cohort, a patient need to be HR positive (ER and / or PR expression ≥10%) and the longest diameter of invasive cancer could not exceed 1cm; The pathological type of immunohistochemistry must meet the following conditions: HER-2 (3+) or HER-2 (0-2 +) with FISH detection is amplified; For patients with invasive lesions on both sides, if both lesions are HER-2 positive and meet the tumor size requirements, then can be enrolled; Has adequate organ function meeting the following criteria: (1) adequate bone marrow function: hemoglobin ≥ 90 g/L (no blood transfusion within 14 days); absolute neutrophil count ≥ 1.5 x 109 /L; platelet count ≥ 100 * 109 /L; (2)adequate liver and kidney function: Alanine Aminotransferase (ALT) ≤ 3×upper limit of normal (ULN), Aspartate Aminotransferase (AST) ≤ 3×ULN, Total Bilirubin (TBIL)≤ 1.5×ULN, serum creatinine ≤ 1×ULN#and with endogenous creatinine clearance rate of >50 ml/min (Cockcroft-Gault formula); LVEF>50%; The patient voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up. Exclusion Criteria: Has received neoadjuvant therapy (include chemotherapy, targeted therapy, radiotherapy or endocrine therapy; Has previous history of additional malignancy, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ; Has metastic (Stage 4) breast cancer; Pregnant or breast feeding women, or women of childbearing age who cannot practice effective contraceptives; Patients participating in other clinical trials at the same time; Has severe organ dysfunction (cardiopulmonary liver and kidney) insufficiency, left ventricular ejection fraction (LVEF) < 50% (cardiac ultrasound); severe cardio cerebral vascular disease within the 6 months previous of randomization (such as unstable angina, chronic heart failure, uncontrolled hypertension with blood pressure>150/90mmHg, myocardial infarction, or cerebral blood vessel); diabetic patients with poor blood glucose control; patients with severe hypertension; Has severe or uncontrolled infection; Has a history of psychotropic substance abuse and were unable to abandon drug habits, or those with history of mental disorders; The researchers considered patients to be unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IRIS-A<br> | Drug: capecitabine and trastuzumab<br>* In IRIS-A cohort, patients who met the inclusion criteria(ER，PR<10%, T≤2cm or ER,PR ≥10% 1cm<T≤2cm）would be given capecitabine for 6 cycles with standard trastuzumab for 1 year, in which HR+ patients would be given endocrine therapy for 5 years.<br>|
| Experimental: IRIS-B<br> | Drug: endocrine therapy and trastuzumab<br>* In IRIS-B cohort, patients who met the inclusion criteria(ER,PR ≥10% T≤1cm) would be given endocrine therapy (premenopausal: tamoxifen or toremifene; postmenopausal: letrozole or anastrozole or exemestane) combined with standard trastuzumab for 1 year and complete endocrine therapy for 5 years.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| iDFS | invasive disease-free survival | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DDFS | distant disease-free survival， | 5 years | 
| OS | overall survival | 5 years |