A PHASE II PROSPECTIVE, TWO-COHORT NON-RANDOMIZED, MULTI-CENTRE, MULTINATIONAL, OPEN LABEL STUDY TO ASSESS THE SAFETY OF ASSISTED- AND SELF-ADMINISTERED SUBCUTANEOUS TRASTUZUMAB AS ADJUVANT THERAPY IN PATIENTS WITH OPERABLE HER2-POSITIVE EARLY BREAST CANCER [SAFEHER STUDY]

Gender: --
Maximum age: 99
Minimum age: 18
Inclusion criteria:
1. SIGNED WRITTEN INFORMED CONSENT APPROVED BY THE REVIEWING INDEPENDENT ETHICS COMMITTEE (EC)
2. FEMALE OR MALE AGED 18 YEARS OR ABOVE
3. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) PERFORMANCE STATUS 0 OR 1
4. HISTOLOGICALLY CONFIRMED EARLY INVASIVE HER2-POSITIVE CARCINOMA OF THE BREAST WITH NO EVIDENCE OF RESIDUAL, LOCALLY RECURRENT OR METASTATIC DISEASE AND DEFINED AS CLINICAL STAGE I (T1, NO, MO) TO WC (ANY T, N3, MO) THAT IS ELIGIBLE FOR ADJUVANT TREATMENT WITH TRASTUZUMAB
NOTE: PATIENTS TREATED WITHOUT NEOADJUVANT OR ADJUVANT CHEMOTHERAPY, SUCH
AS PATIENTS WITH LOW RISK NODE NEGATIVE TUMOURS1.0 CM, ELDERLY PATIENTS (>65 YEARS OF AGE) OR PATIENTS WITH HER2-POSITIVE EBC BUT DENYING CHEMOTHERAPY, WILL ALSO BE ELIGIBLE TO PARTICIPATE IN THE STUDY, BUT THEIR ENROLMENT WILL BE LIMITED TO APPROXIMATELY 10% OF THE TOTAL STUDY POPULATION.
5. HER2-POSITIVE EBC, DEFINED AS IHC 3+, OR FISH/C1SH POSITIVE, AS DETERMINED IN A LOCAL LABORATORY THAT IS EXPERIENCED/CERTIFIED IN HER2- EXPRESSION TESTING USING AN ACCURATE AND VALIDATED ASSAY
6. SCREENING LEFT VENTRICULAR EJECTION FRACTION (LVEF) 55% AS MEASURED BY ECHOCARDIOGRAPHY, MULTI GATED ACQUISITION (MUGA) SCAN OR MAGNETIC RESONANCE IMAGING (MRI) PER LOCAL PRACTICE

Exclusion criteria:
CANCER RELATED CRITERIA:
1. PREVIOUS NEOADJUVANT OR ADJUVANT BREAST CANCER TREATMENT WITH AN APPROVED OR INVESTIGATIONAL ANTI-HER2 AGENT
2. HISTORY OF OTHER MALIGNANCY WHICH COULD AFFECT COMPLIANCE WITH THE PROTOCOL OR INTERPRETATION OF RESULTS. PATIENTS WITH CURATIVELY TREATED CARCINOMA IN SITU OF THE CERVIX OR BASAL CELL CARCINOMA, AND PATIENTS WITH OTHER CURATIVELY-TREATED MALIGNANCIES WHO HAVE BEEN DISEASE-FREE FOR AT LEAST 5 YEARS, ARE ELIGIBLE.
3. PAST HISTORY OF DUCTAL CARCINOMA IN SITU (DCIS) AND/OR LOBULAR CARCINOMA IN SITU (LCIS) THAT HAS BEEN TREATED WITH ANY SYSTEMIC THERAPY OR WITH RADIATION THERAPY TO THE IPSILATERAL BREAST WHERE INVASIVE CANCER SUBSEQUENTLY DEVELOPS. PATIENTS WHO HAD THEIR DCISILCIS TREATED WITH SURGERY ONLY ARE ALLOWED TO ENTER THE STUDY.
4. METASTATIC DISEASE
5. INADEQUATE BONE MARROW FUNCTION (AS INDICATED BY ANY OF THE FOLLOWING):
. TOTAL WHITE BLOOD CELL COUNT (WBC) < 2,5001 MM3 (<2.5 X 10⁹/L)
. ABSOLUTE NEUTROPHIL COUNT (ANC) < 1,5001 MM3 (< 1.5 X 10⁹/L)
. PLATELETS < 100,000 / MM3 (< 100 X 10⁹/L)
. HAEMOGLOBIN < 10 G/DL
6. IMPAIRED HEPATIC FUNCTION (AS INDICATED BY ANY OF THE FOLLOWING):
. SERUM TOTAL BILIRUBIN > 1.5 X UPPER LIMIT OF NORMAL (ULN)
. ALANINE AMINO TRANSFERASE (ALT) AND/OR ASPARTATE AMINO TRANSFERASE (AST) > 1.25 X ULN
. ALKALINE PHOSPHATASE (ALP) > 2.5 X ULN