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

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Pyrotinib; Drug: Pyrotinib in combination with trastuzumab

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 Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • The Second Affiliated hospital of Zhejiang University School of Medical
      • Contact: XianHua Fu, Doctor; Phone Number: 15858222675; Email: fxh198501@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single drug group; Pyrotinib: 400 mg, po, qd, 21d for a treatment cycle	Drug: Pyrotinib; Pyrotinib as interventions were used in patients with HER2-positive advanced colorectal cancer
EXPERIMENTAL: Dual-targeted drug group; 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; Pyrotinib in combination with trastuzumab as interventions were used in patients with HER2-positive advanced colorectal cancer

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Zhejiang Cancer Hospital; First Affiliated Hospital of Zhejiang University; Sir Run Run Shaw Hospital; Zhejiang Provincial People's Hospital

Publications and helpful links

General Publications

• Fu X, Ying J, Yang L, Fang W, Han W, Hu H, Zhang S, Yuan Y. Dual targeted therapy with pyrotinib and trastuzumab for HER2-positive advanced colorectal cancer: A phase 2 trial. Cancer Sci. 2022 Nov 16. doi: 10.1111/cas.15660. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 17, 2019
• Primary Completion (ANTICIPATED): December 17, 2021
• Study Completion (ANTICIPATED): June 17, 2022

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (ACTUAL): May 8, 2020

Study Record Updates

• Last Update Posted (ACTUAL): July 15, 2021
• Last Update Submitted That Met QC Criteria: July 13, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: HER2; Advanced Colorectal Cancer; Pyrotinib
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: IR2019001210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The data were Shared with the sub-center, and the preliminary efficacy results were to be submitted to the tumor conference

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No