A Study Of SIBP-01 Or CN-Trastuzumab Plus Docetaxel And Carboplatin In HER2 Positive Breast Cancer

NCT03989037 | Completed Phase 3 DMC

• 1 other identifier: SIBP-01-3
• Study Type: interventional
• Target: 580
• Locations: 1 country
• Sites: 1

Brief Summary

The study will compare PK, efficacy, safety, and immunogenicity of SIBP-01 (Trastuzumab Biosimilar) in combination with Docetaxel and Carboplatin versus Herceptin® (CN-Trastuzumab) approved in the CN in combination with Docetaxel and Carboplatin in patients with operable HER2 positive, with early or locally advanced HER2-positive breast cancer. The hypothesis to be tested in this study is the tpCR of patients with Cycle 6 of SIBP-01 is similar to CN-approved trastuzumab, using a 90% bilateral confidence interval between 0.74 and 1.5.

Conditions

HER2-positive Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Total pathologic complete response (tpCR)

  Total Pathologic Complete Response (tpCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes(ypT0/is, ypN0). Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response..The tpCR was assessed by the Independent Response Evaluation Committee (IREC)

  at the end of Cycle 6(each cycle is 3 weeks)

Secondary Outcomes (3)

• Breast pathologic complete response (bpCR)

  at the end of Cycle 6(each cycle is 3 weeks)

• Proportion of patients with steady-state trough concentration (Ctrough, ss) > 20 μg/mL

  after 5 cycles of treatment ( before cycle 6, each cycle is 3 weeks)

• PK Evaluation After Multi-Dose Administration

  Cycles 1 through 6 ( each cycle is 3 weeks )

Study Arms (2)

SIBP-01 & Docetaxel & Carboplatin

EXPERIMENTAL

SIBP-01→ Docetaxel→ Carboplatin: injection, every 3 weeks for 18 weeks; SIBP-01: first dose 8mg/kg, then 6mg/kg; Docetaxel: dose 75mg/m2; Carboplatin: dose AUC6

Drug: SIBP-01; Drug: Docetaxel; Drug: Carboplatin

Herceptin & Docetaxel & Carboplatin

ACTIVE COMPARATOR

Herceptin→ Docetaxel→ Carboplatin: injection, every 3 weeks for 18 weeks; Herceptin: first dose 8mg/kg, then 6mg/kg; Docetaxel: dose 75mg/m2; Carboplatin: dose AUC6

Drug: Herceptin; Drug: Docetaxel; Drug: Carboplatin

Interventions

SIBP-01 DRUG

IBP-01: injection; strength: 150mg; first dose 8mg/kg (intravenous infusion, not less than 90 minutes, on the 1st day of each cycle), then 6mg/kg once every 3 weeks, totaling 6 cycles

Also known as: Herceptin Biosimilar

SIBP-01 & Docetaxel & Carboplatin

Herceptin DRUG

Herceptin: injection; strength: 440mg; first dose 8mg/kg (intravenous infusion, not less than 90 minutes, on the 1st day of each cycle), then 6mg/kg once every 3 weeks, totaling 6 cycles

Also known as: Trastuzumab

Herceptin & Docetaxel & Carboplatin

Docetaxel DRUG

Docetaxel: injection; dose 75mg/m2, 75mg/m2 once every 3 weeks (intravenous infusion, not less than 60 minutes, on the 1st day of each cycle), totaling 6 cycles;

Also known as: Docetaxel Injection

Herceptin & Docetaxel & Carboplatin; SIBP-01 & Docetaxel & Carboplatin

Carboplatin DRUG

Carboplatin: injection; dose AUC6, AUC6 once every 3 weeks (intravenous infusion, not less than 30 minutes, on the 1st day of each cycle), totaling 6 cycles;

Also known as: PARAPLATIN®，Carboplatin Injection

Herceptin & Docetaxel & Carboplatin; SIBP-01 & Docetaxel & Carboplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Gender Eligibility Details: Female patients with HER2-positive breast cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Those voluntarily signing the informed consent form, understanding the study and willing to follow all testing procedures;
• Females aged ≥ 18 years and ≤ 75 years (at the date of signing the informed consent form);
• Patients diagnosed with early (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0) invasive breast cancer histologically;
• Patients with HER2-positive breast cancer: HER2 detection is based on the Chinese Breast Cancer HER2 Detection Guidelines (2019 Edition), the immunohistochemistry (IHC) method is used to detect the expression level of HER2 protein, and the in situ hybridization (ISH) method is used to detect the HER2 gene amplification level. ISH includes fluorescence in situ hybridization (FISH) and bright-field in situ hybridization. The common bright-field in situ hybridization method includes chromogenic in situ hybridization (CISH) and silver-enhanced in situ hybridization (SISH);The HER2-positive criterion is: IHC detection +++, or IHC++, and further in situ hybridization confirms that HER2 gene amplification is positive;
• Those planning to receive final surgical resection of breast cancer, i.e. breast-conserving surgery or total mastectomy, sentinel node (SN) biopsy or axillary lymph node dissection (ALND);
• Those planning to receive neoadjuvant chemotherapy;
• Those with the maximum primary tumor diameter of \> 2cm determined by the standard evaluation method of study center (MRI);
• Patients with performance status score of 0 or 1 by the US Eastern Cooperative Oncology Group (ECOG);
• Those with left ventricular ejection fraction (LVEF) of ≥ 55% within 4 weeks prior to randomized enrollment; 10) Those with suitable organs and hematopoietic functions, without significant abnormality in the following laboratory examinations:
• Absolute neutrophil count (NEUT#) ≥1.5×109/L;
• Absolute white blood cell count (WBC) ≥ 3.0 × 109/L;
• Platelet ≥90×109/L;
• Hemoglobin ≥90g/L;
• Serum creatinine ≤1.5 x upper limit of normal (ULN);
• AST and ALT values ≤ 1.5 x ULN;

You may not qualify if:

• Pregnant or lactating women, and patients with positive baseline pregnancy test; women of childbearing age who do not agree to practice abstinence or effective contraception during the study period and within 7 months after the last administration;
• Those with a clear history of drug allergy, especially those with prior severe allergic reaction to macromolecular protein preparation/monoclonal antibody, or to any of the test drug components (NCI-CTCAE 5.0 greater than grade 3);
• Patients with bilateral breast cancer or inflammatory breast cancer;
• Patients with (metastatic) breast cancer Stage IV;
• Those with a history of congestive heart failure, unstable angina, arrhythmia or myocardial infarction;
• Those with other invasive tumors (including second primary breast cancer) that might affect the result evaluation and protocol compliance; however, subjects who are cured with a disease-free survival of at least 5 years may be enrolled;
• Patients with breast cancer who have previously received chemotherapy, endocrine therapy, or anti-HER2 biotherapy, or have received breast surgery (except for diagnostic biopsy of primary breast cancer);
• Those with known, uncontrolled, active bacterial, viral, fungal, mycobacterial, parasitic or other infections (excluding nail bed fungal infection) or with any significant systemic infection event that required intravenous antibiotic treatment or hospitalization (except for neoplastic fever) within 4 weeks prior to enrollment);
• Those with any positive HIV antibody or treponema pallidum antibody;
• Those with active hepatitis B (hepatitis B virus DNA titer is above the lower limit of normal);
• Those with existing, sudden lung disease, interstitial lung disease, pneumonia or pulmonary fibrosis, except for local interstitial pneumonia induced by radiotherapy;
• Those with a prior history of drug abuse, alcohol abuse or drug addiction;
• Those with a clear history of neurological or mental disease and with poor compliance, such as epilepsy and dementia;
• Those with a major surgical operation or infusion of blood or blood components 4 weeks prior to the clinical trial;
• Those with blood loss or donation of more than 400 ml within the 2 months prior to the clinical trial;

Sponsors & Collaborators

• Shanghai Institute Of Biological Products: lead
• Fudan University: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (2)

• Sugitani I, Ueda S, Sakurai T, Shigekawa T, Hirokawa E, Shimada H, Takeuchi H, Matsuura K, Misumi M, Fujiuchi N, Takahashi T, Hasebe T, Osaki A, Saeki T. Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety. Int J Clin Oncol. 2017 Oct;22(5):880-886. doi: 10.1007/s10147-017-1136-8. Epub 2017 May 25.

  PMID: 28547525 RESULT

• Lammers PE, Dank M, Masetti R, Abbas R, Hilton F, Coppola J, Jacobs I. Neoadjuvant PF-05280014 (a potential trastuzumab biosimilar) versus trastuzumab for operable HER2+ breast cancer. Br J Cancer. 2018 Aug;119(3):266-273. doi: 10.1038/s41416-018-0147-1. Epub 2018 Jul 13.

  PMID: 30002437 RESULT

MeSH Terms

Interventions

Trastuzumab; Docetaxel; Carboplatin

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Shanghai Institute Of Biological Products Co., Ltd

  SINOPHARM

  STUDY DIRECTOR

• Fudan University Shanghai Cancer Center

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multi-center, randomized, single-blind, positive drug parallel controlled equivalence clinical trial.

Study Record Dates

• First Submitted: June 14, 2019
• First Posted: June 18, 2019
• Study Start: June 27, 2019
• Primary Completion: April 26, 2023
• Study Completion: April 26, 2023
• Last Updated: December 27, 2023

Record last verified: 2023-12

Locations

CN (1)