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

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

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

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.

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.