Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer

NCT04681911 | Unknown Phase 2 DMC

• 1 other identifier: 2020-KY-125
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

HER2-targeted therapy after the failure of trastuzumab treatment has become a new difficulty and challenge. Inetetamab, a new antibody to optimize the ADCC effect, has become one of the second-line treatment options after trastuzumab fails, showing good survival benefits. Pyrotinib, another second-line HER2 targeted drug, is a typical representative of TKI drugs, which not only has a strong HER2 antagonistic effect but also can synergize with monoclonal antibodies to amplify the ADCC effect. Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. we plan to carry out a phase II single-arm clinical study to evaluate the efficacy and safety of "Inetetamab combined with Pyrotinib and chemotherapy" in the treatment of her positive metastatic breast cancer.

Conditions

Breast Cancer

Keywords

HER2 positive metastatic breast cancer; Inetetamab; Pyrotinib

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate，ORR

  Objective response rate assessed at 18 weeks after enrollment，that is about 6 cycles of treatment

  18 weeks after enrollment

Secondary Outcomes (6)

• Progression Free Survival，PFS

  2 years

• overall survival，OS

  4 years

• Clinical Benefit Rate，CBR

  24 weeks after enrollment

• the rate of adverse events

  up to 24 weeks after enrollment

• Quality of life scale score，QoL

  1 year

Study Arms (1)

Inetetamab Combined With Pyrotinib and Chemotherapy

EXPERIMENTAL

Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle. Pyrotinib: 400mg, oral, every day. Chemotherapy: the choice of physicians，as the following regimens: Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle Carboplatin, AUC = 6, 3-week cycle Albumin paclitaxel, 100 mg/m2, weekly Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle

Drug: Inetetamab; Drug: Pyrotinib; Drug: Capecitabine; Drug: Gemcitabine; Drug: Vinorelbine; Drug: Carboplatin; Drug: Albumin paclitaxel; Drug: Eribulin

Interventions

Inetetamab DRUG

Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.

Inetetamab Combined With Pyrotinib and Chemotherapy

Pyrotinib DRUG

Pyrotinib: 400mg, oral, every day.

Inetetamab Combined With Pyrotinib and Chemotherapy

Capecitabine DRUG

Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle

Also known as: xeloda or other names

Inetetamab Combined With Pyrotinib and Chemotherapy

Gemcitabine DRUG

Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle

Also known as: Gemzar or other names

Inetetamab Combined With Pyrotinib and Chemotherapy

Vinorelbine DRUG

Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle

Also known as: Navelbine or other names

Inetetamab Combined With Pyrotinib and Chemotherapy

Carboplatin DRUG

Carboplatin, AUC = 6, 3-week cycle

Also known as: Paraplatin or other names

Inetetamab Combined With Pyrotinib and Chemotherapy

Albumin paclitaxel DRUG

Albumin paclitaxel, 100 mg/m2, weekly

Also known as: Abraxane or other names

Inetetamab Combined With Pyrotinib and Chemotherapy

Eribulin DRUG

Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle

Also known as: Halaven

Inetetamab Combined With Pyrotinib and Chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must meet all of the following conditions:
• Adult female patients (age 18-70 years) with metastatic breast cancer confirmed by pathology or imaging;
• Pathological diagnosis of HER-2 was positive (definition: immunohistochemical results were + + + or in situ hybridization results were positive);
• Received trastuzumab treatment in the past;
• the patients have received 1-3 treatments for metastatic breast cancer in the past;
• According to RECIST 1.1, patients with at least one target lesion or simple bone metastasis can be evaluated;
• ECoG score of physical status was less than 2, and the expected survival time was not less than 3 months;
• Prior treatment-related toxicity should be reduced to NCI CTCAE (version 5.0) ≤ 1 degree (except for hair loss or other toxicity which is considered as no risk to patient's safety according to the investigator's judgment) 8）LVEF≥50%；
• \) Sufficient functional reserve of bone marrow
• White blood cell count (WBC) ≥ 3.0 × 10 \^ 9 / L,
• Neutrophil count (ANC) ≥ 1.5 × 10 \^ 9 / L,
• Platelet count (PLT) ≥ 100 × 10 \^ 9 / L 10) Previous treatment-related toxicity should be relieved as NCI CTCAE (version 5.0) ≤ 1 degree, total bilirubin (TBIL) ≤ 1.5 × upper limit of normal value (ULN), alanine aminotransferase (ALT / AST) ≤ 2.5 × ULN (liver metastasis patients ≤ 5xuln), serum creatinine ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60 ml / min; 11) Be able to understand the research process, volunteer to participate in the study, and sign informed consent.

You may not qualify if:

• Subjects were not allowed to participate in the study if they had any of the following conditions:
• No trastuzumab treatment was received;
• Have received more than 3 therapeutic regimens for metastatic breast cancer;
• No treatment for metastatic breast cancer was received;
• Patients who are known to be allergic to active or other components of the study drug.
• They received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before enrollment, or were participating in any clinical trials of intervention drugs;
• Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.
• Any other situation in which the researcher considers that the patient is not suitable for the study may interfere with the concomitant diseases or conditions involved in the study, or there are any serious medical barriers that may affect the safety of the subjects (e.g., uncontrollable heart disease, hypertension, active or uncontrollable infection, active hepatitis B virus infection)

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat Sen Memorial Hospital，Sun Yat sen University

Guangzhou, Guangdong, 510000, China

RECRUITING

Related Publications (3)

• Li X, Yang C, Wan H, Zhang G, Feng J, Zhang L, Chen X, Zhong D, Lou L, Tao W, Zhang L. Discovery and development of pyrotinib: A novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor with favorable safety profiles for the treatment of breast cancer. Eur J Pharm Sci. 2017 Dec 15;110:51-61. doi: 10.1016/j.ejps.2017.01.021. Epub 2017 Jan 21.

  PMID: 28115222 RESULT

• Ma F, Ouyang Q, Li W, Jiang Z, Tong Z, Liu Y, Li H, Yu S, Feng J, Wang S, Hu X, Zou J, Zhu X, Xu B. Pyrotinib or Lapatinib Combined With Capecitabine in HER2-Positive Metastatic Breast Cancer With Prior Taxanes, Anthracyclines, and/or Trastuzumab: A Randomized, Phase II Study. J Clin Oncol. 2019 Oct 10;37(29):2610-2619. doi: 10.1200/JCO.19.00108. Epub 2019 Aug 20.

  PMID: 31430226 RESULT

• Ma F, Li Q, Chen S, Zhu W, Fan Y, Wang J, Luo Y, Xing P, Lan B, Li M, Yi Z, Cai R, Yuan P, Zhang P, Li Q, Xu B. Phase I Study and Biomarker Analysis of Pyrotinib, a Novel Irreversible Pan-ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer. J Clin Oncol. 2017 Sep 20;35(27):3105-3112. doi: 10.1200/JCO.2016.69.6179. Epub 2017 May 12.

  PMID: 28498781 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pyrotinib; Capecitabine; Gemcitabine; Vinorelbine; Carboplatin; Albumin-Bound Paclitaxel; eribulin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Coordination Complexes; Organic Chemicals; Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Jianli Zhao

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianli Zhao

CONTACT

86-20-34070870; zhaojli5@mail.sysu.edu.cn

Ying Wang

CONTACT

86-20-34070499; wangy556@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Attending Doctor

Model Details: In order to improve the curative effect and prolong the survival rate, we added Inetetamab to the current second-line treatment regimen of Pyrotinib combined with chemotherapy

Study Record Dates

• First Submitted: October 25, 2020
• First Posted: December 23, 2020
• Study Start: September 9, 2020
• Primary Completion: September 9, 2023
• Study Completion: September 9, 2024
• Last Updated: December 23, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)