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

Phase 2

• Conditions: Colorectal Cancer
• Interventions: Drug: Pyrotinib in combination with trastuzumab; Drug: Pyrotinib

• Registration Number: NCT04380012
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

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.

Study Timeline

• Study Start: 2019-12-17
• Study First Submitted: 2020-02-04
• Study First Submitted QC: 2020-05-06
• Study First Posted: 2020-05-08
• Status Verified: 2021-02
• Last Update Submitted: 2021-07-13
• Last Update Posted: 2021-07-15
• Primary Completion: 2021-12-17
• Study Completion: 2022-06-17

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dual-targeted drug group	Pyrotinib in combination with trastuzumab	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
Single drug group	Pyrotinib	Pyrotinib: 400 mg, po, qd, 21d for a treatment cycle

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	Approximately 24 months	The proportion of patients with complete response or partial response according to RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
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.
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.
Overall Survival	Up to 2 years	Time from the initiation of treatment to any-cause death.
Duration of Response	Approximately 24 months	Time from complete response or partial response to disease progression or any-cause death.

Trial Locations

Locations (1)

The Second Affiliated hospital of Zhejiang University School of Medical; 🇨🇳 Hangzhou, Zhejiang, China