Colorectal Cancer
Conditions
Keywords
HER2, Advanced Colorectal Cancer, Pyrotinib
Brief summary
To Observe the Efficacy and Safety of Pyrotinib Maleate in Patients With HER2-positive Advanced Colorectal Cancer
Detailed description
This study is an investigator-initiated, open-label, two-cohort phase II trial, assessing the objective response rate (ORR) of pyrotinib monotherapy (Cohort 1) or in combination with trastuzumab (Cohort 2), in HER2-positive advanced colorectal cancer. HER2 positivity is centrally established by immunohistochemistry (IHC) and silver in situ hybridization (SISH). To be HER2 eligible the original tumor, or the biopsied metastasis (whichever is last available), must be IHC 3+ or 2+ in more than 50% of cells, confirmed by SISH or fluorescence in situ hybridization (FISH) with a HER2:CEP17 ratio ≥ 2.0. For IHC a positive staining (3+) is defined as an intense membrane staining which can be circumferential, basolateral, or lateral of the tumor cells.
Interventions
DRUGPyrotinib
Pyrotinib as interventions were used in patients with HER2-positive advanced colorectal cancer
DRUGPyrotinib in combination with trastuzumab
Pyrotinib in combination with trastuzumab as interventions were used in patients with HER2-positive advanced colorectal cancer
Sponsors
Zhejiang Cancer Hospital
Zhejiang Provincial People's Hospital
First Affiliated Hospital of Zhejiang University
Sir Run Run Shaw Hospital
Second Affiliated Hospital, School of Medicine, Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Aged 18-75 years, male or female; * 2\. ECOG performance status 0-2; * 3\. Recurrent/metastatic advanced colorectal cancer diagnosed by histology or cytology; * 4\. Patients who progressed on or were intolerable to standard therapy, or those who refused chemotherapy; * 5\. At least one measurable lesion according to RECIST v1.1; * 6\. HER2 positivity (including amplification, mutation, and overexpression) detected by clinically recognized methods (including PCR, FISH, immunohistochemistry, and NGS), and the data obtained by NGS at the pathology department of hospital or qualified gene testing organization could be accepted; * 7.The functional level of the major organs must meet the following requirements (no blood transfusion within 2 weeks prior to screening, no use of leukocytes- or platelet-raising drugs): 1. Blood routine: neutrophils (ANC) ≥ 1.5 × 10\^9 / L; platelet count (PLT) ≥ 90 × 10\^9 / L; hemoglobin (Hb) ≥ 90 g / L; 2. Blood biochemistry: total bilirubin (TBIL) ≤ upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 × ULN（Patients with liver metastases were ≤5 × ULN）; 3. Cardiac color doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 55%; 4. 12-lead electrocardiogram: The QT interval corrected by the Fridericia method (QTcF) \< 470 msec; * 8\. Sign the informed consent and agree to collect the clinical efficacy and information of the patient.
Exclusion criteria
* 1\. The presence of third interstitial effusion (such as a large amount of pleural fluid and ascites) that cannot be controlled by drainage or other methods makes it impossible to evaluate the clinical treatment effect; * 2\. History of substance abuse and cannot be cured or with mental disorders; * 3\. Pregnant or lactating women; patients with fertility who are unwilling or unable to use effective contraception; * 4\. Severe concomitant disease, or unsuitable to participate in this study decided by the investigator. * 5\. Prior use of pyrotinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Approximately 24 months | The proportion of patients with complete response or partial response according to RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 2 years | Time from the initiation of treatment to any-cause death. |
| Disease Control Rate | Approximately 24 months | The proportion of patients with complete response, partial response or stable disease according to RECIST v1.1. |
| Progression-Free Survival | Up to 2 years | Time from the initiation of treatment to disease progression or any-cause death. |
| Duration of Response | Approximately 24 months | Time from complete response or partial response to disease progression or any-cause death. |
| The Incidence of Adverse Events | From the first drug administration to within 28 days for the last treatment | Adverse Events and Serious Adverse Events were graded according to the NCI-CTCAE V5.0. |
Countries
China
Contacts
Primary ContactYing Yuan, Doctor
Backup ContactXianHua Fu, Doctor
Outcome results
None listed