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出境医 / 临床实验 / Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer

Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer

Study Description
Brief Summary:
Trastuzumab resistance, which is a common therapeutic challenge in HER2 positive metastatic breast cancer, is not fully understood. Pyrotinib is an oral tyrosine kinase inhibitor targeting EGFR, HER-2 and HER-4 receptors. More general inhibition of ErbB family with pyrotinib could provide additional benefit. This study is designed to evaluate the efficacy and safety of pyrotinib in combination with capecitabine in patients with HER2 positive locally advanced or metastatic breast cancer who had early failure on or after trastuzumab treatment.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Pyrotinib combined with capecitabine Phase 2

Detailed Description:
A multi-center, one-arm, open label design study, which is planned to enroll 100 patients with trastuzumab-resistant HER2-positive advanced breast cancer.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer
Actual Study Start Date : June 26, 2019
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : May 31, 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: Pyrotinib plus capecitabine
pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)
Drug: Pyrotinib combined with capecitabine
pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.

Outcome Measures
Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Estimated 12 months ]
    From enrollment to progression or death (for any reason)


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Estimated 12 months ]
    Ratio of CR and PR in all subjects

  2. Duration of Response (DOR) [ Time Frame: Estimated 12 months ]
    The first evaluation of CR or PR to progression or death (for any reason)

  3. Clinical Benefit rate (CBR) [ Time Frame: Estimated 12 months ]
    Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects

  4. Overall Survival (OS) [ Time Frame: Estimated 24 months ]
    From enrollment to death (for any reason)

  5. Adverse Events and Serious Adverse Events [ Time Frame: From informed consent through 28 days following treatment completion ]
    Safety


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

Inclusion Criteria:

  1. Pathologically confirmed HER2 positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification
  2. Aged ≥18 and ≤70 years.
  3. ECOG performance status of 0 to 1.
  4. Life expectancy of more than 12 weeks;
  5. At least one measurable lesion exists(RECIST 1.1)
  6. Patients with trastuzumab resistance is defined as follows:

    Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment); Or Progression during or within 6 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment).

  7. At least 4 weeks from the last treatment of trastuzumab or chemotherapy,at least 5 times of t1/2 or 4 weeks from the last treatment of endocrine therapy(the shorter one is preferred)
  8. Known hormone receptor status
  9. For patients with brain metastases, local treatment (including whole cranial radiotherapy, SBRT, etc.) is required and the brain lesions are stable for ≥ 3 months without the need for dexamethasone or mannitol treatment
  10. Patients with adequate organ function before enrollment:

    1. ANC≥1.5×10^9/L
    2. PLT≥100×10^9/L
    3. Hb≥90 g/L
    4. TBIL≤1.5×ULN
    5. ALT and AST≤3×ULN, (ALT and AST≤5×ULN in patients with liver metastases)
    6. Cr≤1.5×ULN and the creatinine clearance rate≥50 mL/min
    7. LVEF ≥ 50%
    8. QTcF < 480 ms
  11. Signed informed consent.

Exclusion Criteria:

  1. Patients with meningeal metastasis and / or spinal cord metastasis;
  2. Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption;
  3. Patients with malignant serious effusion which cannot be controlled by drainage or other methods;
  4. Less than 4 weeks from the last treatment in last clinical trial;
  5. Known dihydropyrimidine dehydrogenase (DPD) deficiency;
  6. Receiving any other antitumor therapy;
  7. History of other malignancy within the last 5 years, except for carcinoma in situ of cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent;
  8. Received radiotherapy, surgery (excluding local puncture) within 4 weeks prior to enrollment; received anti-tumor endocrine therapy after entering the screening period;
  9. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib, neratinib or pyrotinib);
  10. Previous use of capecitabine or capecitabine not tolerated, except that capecitabine efficacy cannot be judged or capecitabine discontinuation for 3 months or more;
  11. Patients with serious heart disease;
  12. Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history;
  13. Known history of neurological or psychiatric disease, including epilepsy or dementia;
  14. Patients during pregnancy or lactation, patients with childbearing potential tested positive in baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
  15. Evidence of significant medical illness that will substantially increase the risk on the participation or completion of the study in the investigator's judgment. Examples included, but not limited to, hypertension, severe diabetes, etc;
  16. Patients not eligible for this study judged by the investigator.
Contacts and Locations

Contacts
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Contact: Xichun Hu, MD, PhD 021-64175590 ycmnankai@126.com

Locations
Layout table for location information
China
Fudan University Shanghai Cancer Center Recruiting
Shanghai, China, 200032
Contact: Xichun Hu, M.D., Ph.D.    64175590 ext 5006    ycmnankai@126.com   
Sponsors and Collaborators
Fudan University
Jiangsu HengRui Medicine Co., Ltd.
Investigators
Layout table for investigator information
Principal Investigator: Xichun Hu Department of Oncology
Tracking Information
First Submitted Date  ICMJE June 27, 2019
First Posted Date  ICMJE June 28, 2019
Last Update Posted Date June 28, 2019
Actual Study Start Date  ICMJE June 26, 2019
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
Progression Free Survival (PFS) [ Time Frame: Estimated 12 months ]
From enrollment to progression or death (for any reason)
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2019)
  • Objective Response Rate (ORR) [ Time Frame: Estimated 12 months ]
    Ratio of CR and PR in all subjects
  • Duration of Response (DOR) [ Time Frame: Estimated 12 months ]
    The first evaluation of CR or PR to progression or death (for any reason)
  • Clinical Benefit rate (CBR) [ Time Frame: Estimated 12 months ]
    Ratio of CR,PR and SD greater than or equal to 24 weeks in all subjects
  • Overall Survival (OS) [ Time Frame: Estimated 24 months ]
    From enrollment to death (for any reason)
  • Adverse Events and Serious Adverse Events [ Time Frame: From informed consent through 28 days following treatment completion ]
    Safety
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 Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer
Official Title  ICMJE Phase II Study of Pyrotinib in Combination With Capecitabine in Patients With Trastuzumab-resistant HER2-positive Advanced Breast Cancer
Brief Summary Trastuzumab resistance, which is a common therapeutic challenge in HER2 positive metastatic breast cancer, is not fully understood. Pyrotinib is an oral tyrosine kinase inhibitor targeting EGFR, HER-2 and HER-4 receptors. More general inhibition of ErbB family with pyrotinib could provide additional benefit. This study is designed to evaluate the efficacy and safety of pyrotinib in combination with capecitabine in patients with HER2 positive locally advanced or metastatic breast cancer who had early failure on or after trastuzumab treatment.
Detailed Description A multi-center, one-arm, open label design study, which is planned to enroll 100 patients with trastuzumab-resistant HER2-positive advanced breast cancer.
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 Metastatic Breast Cancer
Intervention  ICMJE Drug: Pyrotinib combined with capecitabine
pyrotinib 400 mg once daily; Capecitabine 1000 mg/m2 per day on day 1 through 14, every 21 days.
Study Arms  ICMJE Experimental: Pyrotinib plus capecitabine
pyrotinib(400 mg once daily) + capecitabine (2000 mg/m^2 daily, 1000 mg/m^2 BID)
Intervention: Drug: Pyrotinib combined with capecitabine
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: June 27, 2019)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 31, 2022
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Pathologically confirmed HER2 positive patients with locally advanced or metastatic breast cancer: HER2 IHC 3+, or HER2 IHC 2+ and FISH detection gene amplification
  2. Aged ≥18 and ≤70 years.
  3. ECOG performance status of 0 to 1.
  4. Life expectancy of more than 12 weeks;
  5. At least one measurable lesion exists(RECIST 1.1)
  6. Patients with trastuzumab resistance is defined as follows:

    Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment); Or Progression during or within 6 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment).

  7. At least 4 weeks from the last treatment of trastuzumab or chemotherapy,at least 5 times of t1/2 or 4 weeks from the last treatment of endocrine therapy(the shorter one is preferred)
  8. Known hormone receptor status
  9. For patients with brain metastases, local treatment (including whole cranial radiotherapy, SBRT, etc.) is required and the brain lesions are stable for ≥ 3 months without the need for dexamethasone or mannitol treatment
  10. Patients with adequate organ function before enrollment:

    1. ANC≥1.5×10^9/L
    2. PLT≥100×10^9/L
    3. Hb≥90 g/L
    4. TBIL≤1.5×ULN
    5. ALT and AST≤3×ULN, (ALT and AST≤5×ULN in patients with liver metastases)
    6. Cr≤1.5×ULN and the creatinine clearance rate≥50 mL/min
    7. LVEF ≥ 50%
    8. QTcF < 480 ms
  11. Signed informed consent.

Exclusion Criteria:

  1. Patients with meningeal metastasis and / or spinal cord metastasis;
  2. Patients unable to swallow, with chronic diarrhea, intestinal obstruction, or multiple factors that affect drug use and absorption;
  3. Patients with malignant serious effusion which cannot be controlled by drainage or other methods;
  4. Less than 4 weeks from the last treatment in last clinical trial;
  5. Known dihydropyrimidine dehydrogenase (DPD) deficiency;
  6. Receiving any other antitumor therapy;
  7. History of other malignancy within the last 5 years, except for carcinoma in situ of cervix, basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent;
  8. Received radiotherapy, surgery (excluding local puncture) within 4 weeks prior to enrollment; received anti-tumor endocrine therapy after entering the screening period;
  9. Previous or ongoing use of HER2-targeted tyrosine kinase inhibitors (lapatinib, neratinib or pyrotinib);
  10. Previous use of capecitabine or capecitabine not tolerated, except that capecitabine efficacy cannot be judged or capecitabine discontinuation for 3 months or more;
  11. Patients with serious heart disease;
  12. Allergy to pyrotinib; history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired, congenital immunodeficiency disease, or organ transplantation history;
  13. Known history of neurological or psychiatric disease, including epilepsy or dementia;
  14. Patients during pregnancy or lactation, patients with childbearing potential tested positive in baseline pregnancy test, or patients unwilling to take effective contraceptive measures throughout the trial;
  15. Evidence of significant medical illness that will substantially increase the risk on the participation or completion of the study in the investigator's judgment. Examples included, but not limited to, hypertension, severe diabetes, etc;
  16. Patients not eligible for this study judged by the investigator.
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: Xichun Hu, MD, PhD 021-64175590 ycmnankai@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04001621
Other Study ID Numbers  ICMJE HR-BLTN-003
Has Data Monitoring Committee Yes
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 Xichun Hu, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Jiangsu HengRui Medicine Co., Ltd.
Investigators  ICMJE
Principal Investigator: Xichun Hu Department of Oncology
PRS Account Fudan University
Verification Date June 2019

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

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