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

Primary Purpose

Breast Cancer

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Inetetamab
Pyrotinib
Capecitabine
Gemcitabine
Vinorelbine
Carboplatin
Albumin paclitaxel
Eribulin
Sponsored by
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring HER2 positive metastatic breast cancer, Inetetamab, Pyrotinib

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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)

Sites / Locations

  • Sun Yat Sen Memorial Hospital,Sun Yat sen UniversityRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Inetetamab Combined With Pyrotinib and Chemotherapy

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression Free Survival,PFS
The time from the beginning of treatment to the progression or death of the patient
overall survival,OS
The time from the beginning of treatment to the death of the patient
Clinical Benefit Rate,CBR
Clinical Benefit Rate assessed at 24 weeks after enrollment,that is about 8 cycles of treatment
the rate of adverse events
The probability and severity of adverse reactions were analyzed up to 24 weeks after enrollment
Quality of life scale score,QoL
The quality of life score of patients during treatment was analyzed(FACT-B). Performance Status Rating (PSR) was demonstrated for the FACT-B total score, which is the result of the following subscale scores: SWB (the Social / family Well-Being subscale) , EWB (the Emotional Well-Being subscale), AC (Additional Concerns subscale), PWB (the Physical Well-Being subscale), FWB (the Functional Well-Being subscale)
Exploration of biomarkers
Objective to explore the correlation between biomarkers and the ORR. The biomarkers will be test by nest-generation sequence, which include 520 genes and tumor mutation burden, like ERBB2/TP53/PIK3CA/ERBB4/CCND1 and so on.

Full Information

First Posted
October 25, 2020
Last Updated
December 18, 2020
Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
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1. Study Identification

Unique Protocol Identification Number
NCT04681911
Brief Title
Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
Official Title
A Phase II Single-arm Clinical Trial of Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Recruiting
Study Start Date
September 9, 2020 (Actual)
Primary Completion Date
September 9, 2023 (Anticipated)
Study Completion Date
September 9, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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!

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
HER2 positive metastatic breast cancer, Inetetamab, Pyrotinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
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
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Inetetamab Combined With Pyrotinib and Chemotherapy
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Inetetamab
Intervention Description
Inetetamab: 8mg/kg for the first dose, 6mg/kg for the following doses, every 3 weeks for one cycle.
Intervention Type
Drug
Intervention Name(s)
Pyrotinib
Intervention Description
Pyrotinib: 400mg, oral, every day.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
xeloda or other names
Intervention Description
Capecitabine, 1000 mg/m2, d1-d14, 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar or other names
Intervention Description
Gemcitabine, 1000 mg/m2, D1, D8, 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Other Intervention Name(s)
Navelbine or other names
Intervention Description
Vinorelbine, 25-30 mg/m2, D1, D8, 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Other Intervention Name(s)
Paraplatin or other names
Intervention Description
Carboplatin, AUC = 6, 3-week cycle
Intervention Type
Drug
Intervention Name(s)
Albumin paclitaxel
Other Intervention Name(s)
Abraxane or other names
Intervention Description
Albumin paclitaxel, 100 mg/m2, weekly
Intervention Type
Drug
Intervention Name(s)
Eribulin
Other Intervention Name(s)
Halaven
Intervention Description
Eribulin, 1.4 mg/m2, D1, D8, 3-week cycle
Primary Outcome Measure Information:
Title
Objective Response Rate,ORR
Description
Objective response rate assessed at 18 weeks after enrollment,that is about 6 cycles of treatment
Time Frame
18 weeks after enrollment
Secondary Outcome Measure Information:
Title
Progression Free Survival,PFS
Description
The time from the beginning of treatment to the progression or death of the patient
Time Frame
2 years
Title
overall survival,OS
Description
The time from the beginning of treatment to the death of the patient
Time Frame
4 years
Title
Clinical Benefit Rate,CBR
Description
Clinical Benefit Rate assessed at 24 weeks after enrollment,that is about 8 cycles of treatment
Time Frame
24 weeks after enrollment
Title
the rate of adverse events
Description
The probability and severity of adverse reactions were analyzed up to 24 weeks after enrollment
Time Frame
up to 24 weeks after enrollment
Title
Quality of life scale score,QoL
Description
The quality of life score of patients during treatment was analyzed(FACT-B). Performance Status Rating (PSR) was demonstrated for the FACT-B total score, which is the result of the following subscale scores: SWB (the Social / family Well-Being subscale) , EWB (the Emotional Well-Being subscale), AC (Additional Concerns subscale), PWB (the Physical Well-Being subscale), FWB (the Functional Well-Being subscale)
Time Frame
1 year
Title
Exploration of biomarkers
Description
Objective to explore the correlation between biomarkers and the ORR. The biomarkers will be test by nest-generation sequence, which include 520 genes and tumor mutation burden, like ERBB2/TP53/PIK3CA/ERBB4/CCND1 and so on.
Time Frame
the first week after the enrollment

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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%; 9) 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. Exclusion Criteria: 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianli Zhao
Phone
86-20-34070870
Email
zhaojli5@mail.sysu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Wang
Phone
86-20-34070499
Email
wangy556@mail.sysu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianli Zhao
Organizational Affiliation
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat Sen Memorial Hospital,Sun Yat sen University
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianli Zhao
Phone
020-34070870
Email
zhaojli5@mail.sysu.edu.cn
First Name & Middle Initial & Last Name & Degree
Ying Wang
Phone
020-34070499
Email
wangy556@mail.sysu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
As personal information of patients is involved, we decided not to share individual participant data of patients.
Citations:
PubMed Identifier
28115222
Citation
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.
Results Reference
result
PubMed Identifier
31430226
Citation
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.
Results Reference
result
PubMed Identifier
28498781
Citation
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.
Results Reference
result

Learn more about this trial

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

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