Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors
Primary Purpose
Gastrointestinal Tumor, Effect of Drug
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Pyrotinib with or without trastuzumab
Sponsored by
About this trial
This is an interventional treatment trial for Gastrointestinal Tumor focused on measuring pyrotnib, HER2, Gastrointestinal Tumor, Phase II
Eligibility Criteria
Inclusion Criteria:
- Aged ≥18
- ECOG performance status of 0 to 1.
- Life expectancy of more than 12 weeks.
- At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed HER2 positive gastrointestinal tumors who failed prior therapies.
Required laboratory values including following parameters:
ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms
- Signed informed consent.
Exclusion Criteria:
- Subjects with third space fluid that can not be controled by drainage or other methods.
- Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption.
- Less than 4 weeks from the last radiotherapy, chemotherapy, target therapy
- Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study.
- Receiving any other antitumor therapy.
- Known history of hypersensitivity to pyrotinib or any of it components. Ongoing infection (determined by investigator).
- History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
- Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial.
- Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
- Known history of neurological or psychiatric disease, including epilepsy or dementia.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Pyrotinib
Arm Description
Pyrotinib with or without paclitaxel/trastuzumab treatment
Outcomes
Primary Outcome Measures
Objective Response Rate (ORR)
evaluated in the 24th month since the treatment began
Secondary Outcome Measures
Progression Free Survival (PFS)
evaluated in the 24th month since the treatment began
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04960943
Brief Title
Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors
Official Title
Efficacy and Safety of Pyrotinib in Patients With HER2 Positive Refractory or Metastatic Gastrointestinal Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 1, 2020 (Actual)
Primary Completion Date
September 9, 2022 (Anticipated)
Study Completion Date
March 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Targeting human epidermal factor receptor 2 (HER2) therapy have shown the anti-tumor efficacy in patients with HER2-positive gastrointestinal tumors. Pyrotinib is an irreversible small-molecule receptor tyrosine kinase inhibitor targeting both epidermal growth factor receptor (EGFR) and HER2. This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors.
Detailed Description
This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors. Three cohorts were designed for this trial. Cohort 1: patients with gastric cancer or esophageal adenocarcinoma receiving paclitaxel combined with pyrotinib for second-line therapy; Cohort 2: patients with gastric cancer or esophageal adenocarcinoma receiving pyrotinib monotherapy for third-line or posterior line therapy; Cohort 3: patients with colorectal cancer receiving pyrotinib combined with/without trastuzumab for third-line or posterior line therapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastrointestinal Tumor, Effect of Drug
Keywords
pyrotnib, HER2, Gastrointestinal Tumor, Phase II
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Pyrotinib
Arm Type
Experimental
Arm Description
Pyrotinib with or without paclitaxel/trastuzumab treatment
Intervention Type
Drug
Intervention Name(s)
Pyrotinib with or without trastuzumab
Other Intervention Name(s)
pyrotinib with other drugs
Intervention Description
After enrollment, patients of all the three cohorts were given 400 mg/d oral pyrotinib continuously, every 21 days as a cycle; Cohort 1 and 2 : Patients with gastric cancer or esophageal adenocarcinoma were combined with paclitaxel 80 mg/m2, intravenously, once on the first and eighth day. Cohort 3: Patients with colorectal cancer were given trastuzumab at an initial load dose of 8 mg/kg followed by 6 mg/kg every 3 weeks.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
evaluated in the 24th month since the treatment began
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
evaluated in the 24th month since the treatment began
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
overall survival(OS)
Description
evaluated in the 24th month since the treatment began
Time Frame
24 months
Title
time to progression (TTP)
Description
time to progression since the treatment began
Time Frame
24 months
Title
duration of response (DoR)
Description
the time of duration of response
Time Frame
24 months
Title
disease control rate (DCR)
Description
the proportion of patients who had a best response
Time Frame
24 months
Title
Safety and Tolerability
Description
Number of Participants with treatment related Adverse Events as Assessed by CTCAE v5.0
Time Frame
24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged ≥18
ECOG performance status of 0 to 1.
Life expectancy of more than 12 weeks.
At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed HER2 positive gastrointestinal tumors who failed prior therapies.
Required laboratory values including following parameters:
ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms
Signed informed consent.
Exclusion Criteria:
Subjects with third space fluid that can not be controled by drainage or other methods.
Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption.
Less than 4 weeks from the last radiotherapy, chemotherapy, target therapy
Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study.
Receiving any other antitumor therapy.
Known history of hypersensitivity to pyrotinib or any of it components. Ongoing infection (determined by investigator).
History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial.
Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
Known history of neurological or psychiatric disease, including epilepsy or dementia.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodong Xiaodong, phD
Phone
8621-64175590
Email
xddr001@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xiaodong Zhu, phD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenhua Li
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35941028
Citation
Chang J, Xu M, Wang C, Huang D, Zhang Z, Chen Z, Zhu X, Li W. Dual HER2 Targeted Therapy With Pyrotinib and Trastuzumab in Refractory HER2 Positive Metastatic Colorectal Cancer: A Result From HER2-FUSCC-G Study. Clin Colorectal Cancer. 2022 Dec;21(4):347-353. doi: 10.1016/j.clcc.2022.07.003. Epub 2022 Jul 16.
Results Reference
derived
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Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors
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