A Clinical Study of Pyrotinib in Patients With HER2-positive Advanced Colorectal Cancer

Study Overview
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Brief Summary
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To Observe the Efficacy and Safety of Pyrotinib Maleate in Patients With HER2-positive Advanced Colorectal Cancer

Detailed Description
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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.

Official Title
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Pyrotinib Maleate With or Without Trastuzumab in the Treatment of HER2-positive Advanced Colorectal Cancer: a Multicenter Clinical Trial

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Pyrotinib
* Drug: Pyrotinib in combination with trastuzumab


Participation Criteria
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Eligibility Criteria
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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): Blood routine: neutrophils (ANC) ≥ 1.5 × 10^9 / L; platelet count (PLT) ≥ 90 × 10^9 / L; hemoglobin (Hb) ≥ 90 g / L; 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）; Cardiac color doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 55%; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single drug group<br>Pyrotinib: 400 mg, po, qd, 21d for a treatment cycle | Drug: Pyrotinib<br>* Pyrotinib as interventions were used in patients with HER2-positive advanced colorectal cancer<br>|
| Experimental: Dual-targeted drug group<br>Pyrotinib: 400 mg, po, qd, 21d for one treatment cycle; Trastuzumab: first dose 8 mg/kg, then 6 mg/kg, iv, q3w, 21d for one treatment cycle | Drug: Pyrotinib in combination with trastuzumab<br>* Pyrotinib in combination with trastuzumab as interventions were used in patients with HER2-positive advanced colorectal cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The proportion of patients with complete response or partial response according to RECIST v1.1. | Approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | The proportion of patients with complete response, partial response or stable disease according to RECIST v1.1. | Approximately 24 months | 
| Progression-Free Survival | Time from the initiation of treatment to disease progression or any-cause death. | Up to 2 years | 
| Overall Survival | Time from the initiation of treatment to any-cause death. | Up to 2 years | 
| Duration of Response | Time from complete response or partial response to disease progression or any-cause death. | Approximately 24 months | 
| The Incidence of Adverse Events | Adverse Events and Serious Adverse Events were graded according to the NCI-CTCAE V5.0. | From the first drug administration to within 28 days for the last treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pyrotinib, HER2, Advanced Colorectal Cancer