newly diagnosed primary HER2 positive early or locally advanced breast cancer MedDRA version: 18.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 18.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: SB3 (Trastuzumab biosimilar)
Product Code: SB3
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
CAS Number: 180288-69-1
Concentratio
Sponsors
Samsung Bioepis Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female aged 18-65 years 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 3. Non-metastatic, unilateral newly diagnosed primary breast cancer of clinical stage II to III including inflammatory breast cancer with: a. tumour size = 2 cm b. histologically confirmed primary invasive adenocarcinoma of the breast c. HER2-positivity confirmed by a central laboratory or an accredited local laboratory and defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridisation (FISH) +: 4. Known hormone receptor (oestrogen receptor and progesterone receptor) status 5. Baseline LVEF = 55% measured by echocardiography or mmultiple gated acquisition (MUGA) scan 6. Subjects must be able to provide informed consent, which must be obtained prior to any study related procedures 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 498 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Metastatic (stage IV) or bilateral or clinically detectable two separate breast cancer masses by physical examination (palpation). 2. History of any prior invasive breast carcinoma, except for subjects with a past history of ductal carcinoma in situ (DCIS) and/or lobular carcinoma in situ (LCIS) treated with surgery only. 3. Past or current history of malignant neoplasms within 5 years prior to Randomisation, except for curatively treated carcinoma in situ of uterine cervix, basal cell carcinoma of the skin or squamous cell carcinoma of the skin (malignant neoplasm occurring more than 5 years prior to Randomisation are permitted if curatively treated with surgery only) 4. Previous history of radiation therapy (RT), immunotherapy, chemotherapy or biotherapy (including prior HER2 directed therapy) 5. Major surgery within 4 weeks prior to Randomisation and minor surgery within 2 weeks prior to Randomisation (major surgery is defined as surgery which requires general anaesthesia); the diagnostic procedures such as open and/or core-needle biopsies will not be regarded as surgeries mentioned above; SLNB before initiation of neoadjuvant therapy will be exempted from this criterion) 6. Serious cardiac illness that would preclude the use of trastuzumab such as: a. history of documented CHF (NYHA class II or greater heart disease) b. LVEF 180 mmHg and/or diastolic > 100 mmHg) f. clinically significant valvular heart disease g. high risk uncontrolled arrhythmias 7. Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy 8. Known history of HBV (excluding immunized or fully recovered from the past infection), HCV or HIV infection 9. Other concurrent serious illnesses that may interfere with planned treatment including severe cardiovascular, pulmonary, metabolic or infectious conditions 10. Known hypersensitivity to the IPs, non-IPs or any ingredients or excipients of the IPs or non-IPs 11. Known hypersensitivity to murine proteins 12. Known history of dihydropyrimidine dehydrogenase (DPD) deficiency 13. Pre-existing peripheral sensory or motor neuropathy = grade 2, defined by NCI-CTCAE v4.0 14. Any of the following abnormal laboratory tests a. serum total bilirubin > 1.5 × upper limit of normal (ULN); in cases of known Gilberts syndrome, level of total bilirubin within 3 × ULN is permitted b. aspartate transaminase (AST) and/or alanine transaminase (ALT) > 1.5 × ULN c. alkaline phosphatase (ALP) > 2.5 × ULN d. serum creatinine > 1.5 × ULN e. haemoglobin (Hb) < 9 g/dL f. absolute neutrophil count (ANC) < 1500/mm3 (< 1.5 × 109/L) g. platelets count < 100000/mm3 (< 100 × 109/L) 15. Pregnant or lactating women. A pregnancy test result is required for all women of childbearing potential including women who had menopause onset within 2 years prior to Randomisation. Women of childbearing potential must agree to use non-hormonal contraceptive methods (see section 7.4.2.) during the study and 7 months after the last dose IP 16. Concurrent hormonal therapy including birth control pills, ovarian hormone replacement for menopause, selective oestrogen receptor modulator (SERM) either for osteoporosis or breast cancer prevention 17. Subjects unwilling to follow the study requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Study week 24;Secondary Objective: * To evaluate the efficacy of SB3 compared to Herceptin® by - total pathological complete response (tpCR) rate - overall clinical response rate - event-free survival - overall survival * To evaluate the safety and tolerability of SB3 compared to Herceptin® *To evaluate the pharmacokinetics of SB3 compared to Herceptin® * To evaluate the immunogenicity of SB3 compared to Herceptin®;Main Objective: The primary objective of this study is to demonstrate comparable clinical efficacy of SB3 to Herceptin®, in terms of Pathologic complete response rate of the primary breast tumour in women with HER2 positive Early breast cancer or Locally advanced breast cancer in neoadjuvant setting.;Primary end point(s): The Pathologic complete response rate of the primary breast tumour | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Total pathologic complete response, defined as the absence of invasive residual in both breast and lymph nodes • Overall clinical response rate during neoadjuvant therapy (tumour size will be measured by ultrasound or caliper) • Event-free survival (EFS), defined as the time from the date of randomisation to the date where an event occurs. An event is disease recurrence or progression (local, regional, distant or contralateral) or death due to any cause • Overall survival (OS), defined as the time from the date of randomisation to the date of death, regardless of the cause of death. Subjects who were alive at the time of analysis will be censored at the date of the last follow up assessment;Timepoint(s) of evaluation of this end point: Measured at various intervals in the study from beginning to end as per Protocol. | — |
Countries
Bulgaria, Czech Republic, India, Korea, Republic of, Mexico, Philippines, Poland, Romania, Russian Federation, Ukraine, United Kingdom
Contacts
Public ContactQuintiles Contact Centre
Quintiles Limited
Outcome results
None listed