HER2-Positive Early Breast Cancer MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Medica Scientia Innovation Research (MedSIR)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to beginning specific protocol procedures. 2. Female or male patients = 18 years of age. 3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 4. Histologically proven invasive carcinoma of the breast. 5. Tumor size between >5 to 25 mm using breast MRI and node-negative status by clinical exam, MRI and ultrasound. 6. Centrally confirmed HER2[+] disease (IHC score 3+). 7. Known estrogen receptor (ER) and progesterone receptor (PgR) status locally determined prior to study entry. 8. Normal left ventricular function and diastolic function (left ventricular ejection fraction [LVEF] =55%) as assessed by echocardiogram or multiple-gated acquisition scan (MUGA) documented within =28 days prior to first dose of study treatment. 9. Adequate bone marrow, liver, and renal function: a. Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) = 1.5 x 109/L, platelet count = 100.0 x109/L, and hemoglobin = 10.0 g/dL (= 6.2 mmol/L). b. Hepatic: total bilirubin = institutional upper limit of normal (ULN) (except for Gilbert’s syndrome); alkaline phosphatase (ALP) = 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) = 1.5 times ULN. c. Renal: serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 10. Patient must be accessible for treatment and follow-up. 11. Willingness and ability to provide blood samples at baseline, after 2 treatment cycles and at surgery. 12. Willingness to provide tumor tissue samples at baseline and at surgery. 13. All patients must be willing to undergo a pulmonary (X-ray or CT scan), hepatic (ultrasound or CT scan) and bone (PET or CT scan) assessment, to prove no evidence of metastatic disease. 14. Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of nonhormonal contraception or 2 effective forms of nonhormonal contraception by the patient and/or partner and to continue its use for the duration of study treatment and for 7 months after the last dose of study treatment. Note: Acceptable forms of effective contraception should include 2 of the following: i. Placement of non-hormonal intrauterine device (IUD) ii. Condom with spermicidal foam/gel/film/cream/suppository iii. Diaphragm or cervical/vault caps with spermicidal foam/film/cream/suppository The above contraception is not a requirement in the case the male patient, or male partner of a female patient, is surgically sterilized, the female patient is > 45 years of age and is postmenopausal (has not menstruated for at least 12 consecutive months) or the patient remains abstinent and truly abstains from sexual activity (refrains from heterosexual intercourse). 15. Negative serum pregnancy test for premenopausal women including women who have had a tubal ligation and for women less than 12 months after the onset of menopause Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 393 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 393
Exclusion criteria
Exclusion criteria: 1. Any previous treatment, including chemotherapy, anti-HER2 therapy, radiation therapy, or ET for invasive breast cancer, except for breast carcinoma in situ of the contralateral breast cancer, in the last 5 years 2. HER2 0+, 1+ or 2+ despite in situ hybridization (ISH) positive. 3. Node-positive HER2[+] breast cancer 4. Evidence of metastatic disease. Note: CT/MRI scan of thorax/abdomen/pelvis to rule out metastatic disease will be performed before enrolment. 5. Known hypersensitivity reaction to any investigational or therapeutic compound or their incorporated substances. 6. History of other malignancy within the last five years prior to first dose of study drug administration, except for curatively treated basal and squamous cell carcinoma of the skin and/or in situ cervical carcinoma. 7. Uncontrolled hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg) despite adequate antihypertensive treatment. 8. Serious cardiac illness or medical conditions including, but not confined to, the following: - History of NCI CTCAE v5.0 Grade = 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class = II. - High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate = 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second-degree AV-block Type 2 [Mobitz II] or third-degree AV-block). - Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication. - Angina pectoris requiring anti-angina medication. - Clinically significant valvular heart disease. - Evidence of transmural infarction on electrocardiogram (ECG). - Evidence of myocardial infarction within 12 months prior to randomization. 9. History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalaemia, hypomagnesemia, hypocalcaemia), or family history of sudden unexplained death or long QT syndrome. 10. Active uncontrolled infection at the time of enrollment. 11. Current known infection with HIV, hepatitis B virus, or hepatitis C virus. 12. Patients with pulmonary disease requiring continuous oxygen therapy. 13. Current NCI CTCAE (version v5.0) Grade =2 neuropathy. 14. Previous history of bleeding diathesis. 15. Patient is currently receiving chronic treatment with corticosteroids, or another immunosuppressive agent (standard premedication for chemotherapy and local applications are allowed). 16. Major surgical procedure or significant traumatic injury within 14 days prior to randomization or anticipation of need for major surgery within the course of the study treatment. 17. LVEF below 55% as determined by multiple-gated acquisition (MUGA) scan or echocardiography (ECHO). 18. Any other concurrent severe and/or uncontrolled medical condition that would contraindicate patient participation in the clinical study. 19. History of receiving any investigational treatment within 28 days prior to randomization. 20. Pregnant or breast-feeding women or patients not willing to apply highly effective contraception as defined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary efficacy objective ?To assess 3-year recurrence-free interval (3y-RFI) in patients with previously untreated HER2[+] (IHC3+) node-negative early stage breast cancer. Primary safety objective ?To assess global health status decline rate at 1 year from start of neoadjuvant treatment.;Secondary Objective: ?To assess overall efficacy by pathologic complete response ?To compare rate of pCR by HR status ?To evaluate residual cancer burden (RCB) and rate of breast-conserving surgery (BCS) ?To evaluate correlation between final MRI results and BCS, pCR, and RCB at surgery. ?To analyze rate of event-free survival (EFS), relapse-free survival (RFS), invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) at 3 years ?To analyze rate of EFS, RFI, RFS, iDFS, DRFS, DFS, OS, and BCSS at 5 years ?To assess cardiac toxicity profile after 1 year of adjuvant treatment according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v.5.0) ?To assess the general toxicity profile according to CTCAE v.5.0 ?To evaluate QoL as assessed by EORTC-QLC-C30 and QLQ-BR23 scales ?To evaluate ratio of patients who have needed chemotherapy;Primary end point(s): Primary efficacy endpoint ? 3y-RFI defined as time from start of treatment in adjuvant setting until recurrence, new invasive disease, or death from breast cancer. Recurrence will be defined in accordance with the standardized efficacy endpoints (STEEP) criteria. Primary safety endpoint ? Global health status decline rate at 1 year from start of neoadjuvant treatment, defined as the rate of patients with a =10% global health status decline at 1 year from start of neoadjuvant treatment as assessed by the Global Health Status/QoL EORTC-QLC-C30 scale and its breast cancer module QLQ-BR23.;Timepoint(s) of evaluation of this end point: - 3 years recurrence-free Interval | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? pCR rates in the overall population. ? pCR rates according to HR status. ? RCB score. ? Rate of BCS. ? MRI-guided response rate and by BCS, pCR, and RCB. ? 3-year and 5-year EFS, RFI, RFS, iDFS, DRFS, DFS, OS and BCSS. ? AEs reporting including toxicity and safety evaluation at 3 and 5 years. ? QoL assessment (EORTC-QLC-C30 and QLQ-BR23 scales);Timepoint(s) of evaluation of this end point: - 3 years recurrence-free Interval . - Global health status decline rate at 1 year from start of neoadjuvant treatment. | — |
Countries
Spain, United Kingdom
Contacts
Public ContactGustavo Blasco
Medica Scientia Innovation Research (MedSIR)
Outcome results
None listed