A Study to Compare the Effect of SB3 and Herceptin® in Women With HER2 Positive Breast Cancer

NCT ID: NCT02149524

Last Updated: 2018-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 875 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2017-02-28

Brief Summary

A Phase III Randomised, Double-Blind, Parallel Group, Multicentre Study to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity between SB3 (proposed trastuzumab biosimilar) and Herceptin® in Women with Newly Diagnosed HER2 Positive Early or Locally Advanced Breast Cancer in Neoadjuvant Setting

Conditions

HER2 Positive Early or Locally Advanced Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Herceptin (trastuzumab)

Intravenous administration

Group Type: ACTIVE_COMPARATOR

Herceptin (trastuzuamb)

Intervention Type: DRUG

Intravenous administration

SB3 (proposed trastuzumab biosimilar)

Intravenous administration

Group Type: EXPERIMENTAL

SB3 (proposed trastuzumab biosimilar)

Intervention Type: DRUG

Intravenous administration

Interventions

Herceptin (trastuzuamb)

Intravenous administration

Intervention Type: DRUG

SB3 (proposed trastuzumab biosimilar)

Intravenous administration

Intervention Type: DRUG

Other Intervention Names

Herceptin

Eligibility Criteria

Inclusion Criteria

• Female aged 18-65 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Non-metastatic, unilateral newly diagnosed primary breast cancer of clinical stage II to III including inflammatory breast cancer with:

1. tumour size ≥ 2 cm

2. histologically confirmed primary invasive carcinoma of the breast

3. HER2-positivity confirmed by a central laboratory or an accredited local laboratory and defined as immunohistochemistry (IHC) 3+ or fluorescence in situ hybridisation (FISH)+

• Known hormone receptor (oestrogen receptor and progesterone receptor) status
• Baseline left ventricular ejection fraction (LVEF) ≥ 55% measured by echocardiography or multiple gated acquisition (MUGA) scan
• Subjects must be able to provide informed consent, which must be obtained prior to any study related procedures

Exclusion Criteria

• Metastatic (stage IV) or bilateral or multifocal/multicentric breast cancer
• 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
• 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 neoplasms occurring more than 5 years prior to Randomisation are permitted if curatively treated with surgery only)
• Previous history of radiation therapy, immunotherapy, chemotherapy or biotherapy (including prior HER2 directed therapy) 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)
• Serious cardiac illness that would preclude the use of trastuzumab such as:

1. history of documented congestive heart failure (CHF) (New York Heart Association, NYHA, class II or greater heart disease)

2. LVEF < 55% by echocardiography or MUGA scan

3. angina pectoris requiring anti-anginal medication

4. evidence of transmural infarction on electrocardiogram (ECG)

5. uncontrolled hypertension (systolic > 180 mmHg and/or diastolic > 100 mmHg)

6. clinically significant valvular heart disease

7. high risk uncontrolled arrhythmias

• Serious pulmonary illness enough to cause dyspnoea at rest or requiring supplementary oxygen therapy
• Known history of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infection
• Other concurrent serious illnesses that may interfere with planned therapy including severe cardiovascular, pulmonary, metabolic or infectious conditions
• Known hypersensitivity to the investigational product (IPs), non-IPs or any of the ingredients or excipients of the IPs or non-IPs
• Known hypersensitivity to murine proteins
• Known history of dihydropyrimidine dehydrogenase (DPD) deficiency
• Pre-existing peripheral sensory or motor neuropathy ≥ grade 2, defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0
• 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 contraceptive methods (see section 7.4.2) during the study and 6 months after the last dose of IP
• Concurrent hormonal therapy including birth control pills, ovarian hormone replacement for menopause, selective oestrogen receptor modulator (SERM) either for osteoporosis or breast cancer prevention
• Subjects unwilling to follow the study requirements

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Samsung Bioepis Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xavier Pivot

Role: PRINCIPAL_INVESTIGATOR

CHU Besançon Hopital Jean Minjoz Service d'Oncologie Medicale

Locations

Investigational Site

Prague, , Czechia

Countries

Czechia

References

Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Shparyk Y, Moiseyenko V, Bello M 3rd, Semiglazov V, Lee Y, Lim J. A phase III study comparing SB3 (a proposed trastuzumab biosimilar) and trastuzumab reference product in HER2-positive early breast cancer treated with neoadjuvant-adjuvant treatment: Final safety, immunogenicity and survival results. Eur J Cancer. 2018 Apr;93:19-27. doi: 10.1016/j.ejca.2018.01.072. Epub 2018 Feb 12.

Reference Type: DERIVED

PMID: 29448072 (View on PubMed)

Pivot X, Bondarenko I, Nowecki Z, Dvorkin M, Trishkina E, Ahn JH, Vinnyk Y, Im SA, Sarosiek T, Chatterjee S, Wojtukiewicz MZ, Moiseyenko V, Shparyk Y, Bello M 3rd, Semiglazov V, Song S, Lim J. Phase III, Randomized, Double-Blind Study Comparing the Efficacy, Safety, and Immunogenicity of SB3 (Trastuzumab Biosimilar) and Reference Trastuzumab in Patients Treated With Neoadjuvant Therapy for Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer. J Clin Oncol. 2018 Apr 1;36(10):968-974. doi: 10.1200/JCO.2017.74.0126. Epub 2018 Jan 26.

Reference Type: DERIVED

PMID: 29373094 (View on PubMed)

Other Identifiers

2013-004172-35

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SB3-G31-BC

Identifier Type: -

Identifier Source: org_study_id