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

NCT ID: NCT04681911

Last Updated: 2020-12-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 71 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-09
• Study Completion Date: 2024-09-09

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.

Detailed Description

Trastuzumab is the first target drug for HER2 positive metastatic breast cancer, which can significantly improve the survival of patients with HER2 positive metastatic breast cancer and become the first-line standard treatment. However, the selection of second-line targeted drugs after the failure of trastuzumab treatment has become a new difficulty and challenge. Studies have shown that the ADCC effect is one of the main mechanisms of the anti-tumor effect of trastuzumab. Therefore, 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. As two important class 1.1 innovative drugs in China, Pyrotinib and Inetetamab showed excellent anti-tumor efficacy and good safety in TKI and optimized ADCC respectively. Considering that the current guidelines recommend the combination of multiple anti-HER2 targeted drugs, and basic research also shows that Pyrotinib and Inetetamab have a synergistic effect, 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, so as to provide better results for patients with HER2 positive metastatic breast cancer Treatment options!

Conditions

Breast Cancer

Keywords

HER2 positive metastatic breast cancer; Inetetamab; Pyrotinib

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Inetetamab Combined With Pyrotinib and Chemotherapy

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

Group Type: EXPERIMENTAL

Inetetamab

Intervention Type: DRUG

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

Pyrotinib

Intervention Type: DRUG

Pyrotinib: 400mg, oral, every day.

Capecitabine

Intervention Type: DRUG

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

Gemcitabine

Intervention Type: DRUG

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

Vinorelbine

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

Carboplatin, AUC = 6, 3-week cycle

Albumin paclitaxel

Intervention Type: DRUG

Albumin paclitaxel, 100 mg/m2, weekly

Eribulin

Intervention Type: DRUG

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

Interventions

Inetetamab

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

Intervention Type: DRUG

Pyrotinib

Pyrotinib: 400mg, oral, every day.

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Gemcitabine

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

Intervention Type: DRUG

Vinorelbine

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

Intervention Type: DRUG

Carboplatin

Carboplatin, AUC = 6, 3-week cycle

Intervention Type: DRUG

Albumin paclitaxel

Albumin paclitaxel, 100 mg/m2, weekly

Intervention Type: DRUG

Eribulin

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

Intervention Type: DRUG

Other Intervention Names

xeloda or other names; Gemzar or other names; Navelbine or other names; Paraplatin or other names; Abraxane or other names; Halaven

Eligibility Criteria

Inclusion Criteria

Subjects must meet all of the following conditions:

1. Adult female patients (age 18-70 years) with metastatic breast cancer confirmed by pathology or imaging;

2. Pathological diagnosis of HER-2 was positive (definition: immunohistochemical results were + + + or in situ hybridization results were positive);

3. Received trastuzumab treatment in the past;

4. the patients have received 1-3 treatments for metastatic breast cancer in the past;

5. According to RECIST 1.1, patients with at least one target lesion or simple bone metastasis can be evaluated;

6. ECoG score of physical status was less than 2, and the expected survival time was not less than 3 months;

7. 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%；

9) Sufficient functional reserve of bone marrow

1. White blood cell count (WBC) ≥ 3.0 × 10 ^ 9 / L,

2. Neutrophil count (ANC) ≥ 1.5 × 10 ^ 9 / L,

3. 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.

Exclusion Criteria

Subjects were not allowed to participate in the study if they had any of the following conditions:

1. No trastuzumab treatment was received;

2. Have received more than 3 therapeutic regimens for metastatic breast cancer;

3. No treatment for metastatic breast cancer was received;

4. Patients who are known to be allergic to active or other components of the study drug.

5. They received radiotherapy, chemotherapy, endocrine therapy within 4 weeks before enrollment, or were participating in any clinical trials of intervention drugs;

6. Pregnant or lactating women, women of childbearing age who refused to take effective contraceptive measures during the study period.

7. 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

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

OTHER

Sponsor Role: lead

Responsible Party

Jianli Zhao

Attending Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jianli Zhao

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Sun Yat Sen Memorial Hospital，Sun Yat sen University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianli Zhao

Role: CONTACT

Phone: 86-20-34070870

Email: zhaojli5@mail.sysu.edu.cn

Ying Wang

Role: CONTACT

Phone: 86-20-34070499

Email: wangy556@mail.sysu.edu.cn

Facility Contacts

Jianli Zhao

Role: primary

Ying Wang

Role: backup

References

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.

Reference Type: RESULT

PMID: 28115222 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31430226 (View on PubMed)

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.

Reference Type: RESULT

PMID: 28498781 (View on PubMed)

Other Identifiers

2020-KY-125

Identifier Type: -

Identifier Source: org_study_id