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出境医 / 临床实验 / Phase Ⅱ Study of Pegylated Liposomal Doxorubicin(PLD)Plus Trastuzumab in HER-2 Positive Metastatic Breast Cancer

Phase Ⅱ Study of Pegylated Liposomal Doxorubicin(PLD)Plus Trastuzumab in HER-2 Positive Metastatic Breast Cancer

Study Description
Brief Summary:
This is a single-center phase Ⅱ study designed to evaluated the efficacy and safety of pegylated liposomal doxorubicin(PLD)in combination with trastuzumab in HER-2 positive metastatic breast cancer .

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Drug: pegylated liposomal doxorubicin Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ⅱ Study of Pegylated Liposomal Doxorubicin(PLD)Plus Trastuzumab in HER-2 Positive Metastatic Breast Cancer
Actual Study Start Date : March 11, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : May 1, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: PLD in combination with trastuzumab

Trastuzumab: administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg once every 21 days.

pegylated liposomal doxorubicin(PLD):administered at dose of 35mg/m2 IV once every 21 days.

Drug: pegylated liposomal doxorubicin
Eligible patients will be treated with the PLD+trastuzumab regimen until the disease progresses or intolerable toxicity

Outcome Measures
Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: approximately 6 months ]
    The ORR will be calculated as the proportion of patients in the Efficacy Evaluable Patient Set who achieve complete response (CR) and partial response (PR)


Secondary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: approximately 1.5 years ]
    PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause

  2. Incidence and Severity of adverse events [ Time Frame: approximately 1.5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and voluntarily receive the research procedures according to protocol,willingness to sign the written informed consent document;
  • Female patients aged from 18 to 70 years old;
  • Histologically confirmed as invasive breast cancer;
  • HER-2 Positive(defined by: IHC 3+ or ISH positive), regardless of HR status;
  • Recurrence after adjuvant therapy or metastatic breast cancer,and chemotherapy naïve in the metastatic setting or had one prior regimen for metastatic breast cancer;
  • Patients must have measurable disease according to RECIST criteria Version 1.1(Brain metastases lesions and bone metastases lesions were excluded);
  • The adverse event caused by prior therapy has recovered, or stabilized, or does not affect the study administration according to the investigator's judgment;
  • Performance status 0-1;
  • Life expectancy of at least 3 months;
  • Left ventricular ejection fraction (LVEF)≥55%;
  • Brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were in the normal range;
  • Patients must have normal ECG;
  • Bone marrow function: absolute neutrophil count (ANC)≥1.5×109/L,platelets≥100×109/L,hemoglobin ≥90g/L;
  • Hepatic function:alanine aminotransferase(ALT) and aspartate aminotransferase(AST) ≤2.5×ULN,serum total bilirubin≤ 1.5×ULN,or ≤2.5×ULN who has Gilbert's syndrome;
  • Renal function:serum creatinine≤1.5×ULN;
  • Coagulation function:the international standardized ratio (INR) ≤1.5×ULN, prothrombin time (PT) or the activated partial thrombin time (APTT) ≤1.5×ULN.

Exclusion Criteria:

  • Patients with symptomatic brain metastases.
  • Patients who are known or suspected to be allergic to the active ingredient or excipients of the investigational drug.
  • Prior cumulative dose of 240 mg/m2 for doxorubicin and 400 mg/m2 for epirubicin.
  • Prior treatment with anthracyclines has caused cardiotoxicity, or failed (disease progression during therapy or recurrence and metastasis within 12 months after adjuvant therapy).
  • Prior mediastinal radiotherapy.
  • Participation in other clinical trials within 4 weeks before enrollment.
  • Severe cardiovascular disease, including history of congestive heart failure, acute myocardial infarction within 6 months before enrollment, transmural myocardial infarction measured by ECG, uncontrolled arrhythmia, angina requiring therapy, clinically significant valvular heart disease, uncontrolled hypertension.
  • Severe or uncontrolled infection.
  • Positivity for HIV, Hepatitis B or C.
  • Active malignancy in the past 5 years (other than carcinoma in situ of the cervix or basal cell carcinoma of the skin).
  • Patients who are pregnant , breastfeeding ,or refuse to use adequate contraception during the course of participation.
  • Need to concurrent other cancer therapy(other than palliative care for non-target lesions).
  • Other ineligible conditions according to the researcher's judgment.
Contacts and Locations

Contacts
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Contact: peng yuan, Prof 13501270834 ext 13501270834 yuanpeng01@hotmail.com

Locations
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China, Beijing
Peng Yuan Recruiting
Beijing, Beijing, China, 100021
Contact: peng yuan, Prof    13501270834 ext 13501270834    yuanpeng01@hotmail.com   
Contact: xue wang, Dr    13811967690 ext 13501270834    wxyxuki@163.com   
Sponsors and Collaborators
Chinese Academy of Medical Sciences
CSPC Ouyi Pharmaceutical Co., Ltd.
Investigators
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Principal Investigator: peng yuan Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Tracking Information
First Submitted Date  ICMJE April 29, 2019
First Posted Date  ICMJE May 1, 2019
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE March 11, 2019
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
Objective response rate (ORR) [ Time Frame: approximately 6 months ]
The ORR will be calculated as the proportion of patients in the Efficacy Evaluable Patient Set who achieve complete response (CR) and partial response (PR)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Progression-free survival (PFS) [ Time Frame: approximately 1.5 years ]
    PFS will be defined as the time from first dose of study drug until documentation of disease progression or death from any cause
  • Incidence and Severity of adverse events [ Time Frame: approximately 1.5 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase Ⅱ Study of Pegylated Liposomal Doxorubicin(PLD)Plus Trastuzumab in HER-2 Positive Metastatic Breast Cancer
Official Title  ICMJE Phase Ⅱ Study of Pegylated Liposomal Doxorubicin(PLD)Plus Trastuzumab in HER-2 Positive Metastatic Breast Cancer
Brief Summary This is a single-center phase Ⅱ study designed to evaluated the efficacy and safety of pegylated liposomal doxorubicin(PLD)in combination with trastuzumab in HER-2 positive metastatic breast cancer .
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE HER2-positive Breast Cancer
Intervention  ICMJE Drug: pegylated liposomal doxorubicin
Eligible patients will be treated with the PLD+trastuzumab regimen until the disease progresses or intolerable toxicity
Study Arms  ICMJE Experimental: PLD in combination with trastuzumab

Trastuzumab: administered at a loading dose of 8 mg/kg IV followed by 6 mg/kg once every 21 days.

pegylated liposomal doxorubicin(PLD):administered at dose of 35mg/m2 IV once every 21 days.

Intervention: Drug: pegylated liposomal doxorubicin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2019)
30
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 1, 2022
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability to understand and voluntarily receive the research procedures according to protocol,willingness to sign the written informed consent document;
  • Female patients aged from 18 to 70 years old;
  • Histologically confirmed as invasive breast cancer;
  • HER-2 Positive(defined by: IHC 3+ or ISH positive), regardless of HR status;
  • Recurrence after adjuvant therapy or metastatic breast cancer,and chemotherapy naïve in the metastatic setting or had one prior regimen for metastatic breast cancer;
  • Patients must have measurable disease according to RECIST criteria Version 1.1(Brain metastases lesions and bone metastases lesions were excluded);
  • The adverse event caused by prior therapy has recovered, or stabilized, or does not affect the study administration according to the investigator's judgment;
  • Performance status 0-1;
  • Life expectancy of at least 3 months;
  • Left ventricular ejection fraction (LVEF)≥55%;
  • Brain natriuretic peptide (BNP) and cardiac troponin T (cTnT) were in the normal range;
  • Patients must have normal ECG;
  • Bone marrow function: absolute neutrophil count (ANC)≥1.5×109/L,platelets≥100×109/L,hemoglobin ≥90g/L;
  • Hepatic function:alanine aminotransferase(ALT) and aspartate aminotransferase(AST) ≤2.5×ULN,serum total bilirubin≤ 1.5×ULN,or ≤2.5×ULN who has Gilbert's syndrome;
  • Renal function:serum creatinine≤1.5×ULN;
  • Coagulation function:the international standardized ratio (INR) ≤1.5×ULN, prothrombin time (PT) or the activated partial thrombin time (APTT) ≤1.5×ULN.

Exclusion Criteria:

  • Patients with symptomatic brain metastases.
  • Patients who are known or suspected to be allergic to the active ingredient or excipients of the investigational drug.
  • Prior cumulative dose of 240 mg/m2 for doxorubicin and 400 mg/m2 for epirubicin.
  • Prior treatment with anthracyclines has caused cardiotoxicity, or failed (disease progression during therapy or recurrence and metastasis within 12 months after adjuvant therapy).
  • Prior mediastinal radiotherapy.
  • Participation in other clinical trials within 4 weeks before enrollment.
  • Severe cardiovascular disease, including history of congestive heart failure, acute myocardial infarction within 6 months before enrollment, transmural myocardial infarction measured by ECG, uncontrolled arrhythmia, angina requiring therapy, clinically significant valvular heart disease, uncontrolled hypertension.
  • Severe or uncontrolled infection.
  • Positivity for HIV, Hepatitis B or C.
  • Active malignancy in the past 5 years (other than carcinoma in situ of the cervix or basal cell carcinoma of the skin).
  • Patients who are pregnant , breastfeeding ,or refuse to use adequate contraception during the course of participation.
  • Need to concurrent other cancer therapy(other than palliative care for non-target lesions).
  • Other ineligible conditions according to the researcher's judgment.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: peng yuan, Prof 13501270834 ext 13501270834 yuanpeng01@hotmail.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03933319
Other Study ID Numbers  ICMJE CSPC-DMS-BC-11
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Peng Yuan, Chinese Academy of Medical Sciences
Study Sponsor  ICMJE Chinese Academy of Medical Sciences
Collaborators  ICMJE CSPC Ouyi Pharmaceutical Co., Ltd.
Investigators  ICMJE
Principal Investigator: peng yuan Cancer Institute and Hospital, Chinese Academy of Medical Sciences
PRS Account Chinese Academy of Medical Sciences
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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