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

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04380012

Collaborator

Zhejiang Cancer Hospital (Other), Zhejiang Provincial People's Hospital (Other), First Affiliated Hospital of Zhejiang University (Other), Sir Run Run Shaw Hospital (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: Pyrotinib Drug: Pyrotinib in combination with trastuzumab	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 17, 2019

Anticipated Primary Completion Date :

Dec 17, 2021

Anticipated Study Completion Date :

Jun 17, 2022

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Aged 18-75 years, male or female;
1. ECOG performance status 0-2;
1. Recurrent/metastatic advanced colorectal cancer diagnosed by histology or cytology;
1. Patients who progressed on or were intolerable to standard therapy, or those who refused chemotherapy;
1. At least one measurable lesion according to RECIST v1.1;
1. 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;

1. 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;
1. History of substance abuse and cannot be cured or with mental disorders;
1. Pregnant or lactating women; patients with fertility who are unwilling or unable to use effective contraception;
1. Severe concomitant disease, or unsuitable to participate in this study decided by the investigator.
1. Prior use of pyrotinib.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Second Affiliated hospital of Zhejiang University School of Medical	Hangzhou	Zhejiang	China	310009

Sponsors and Collaborators

Second Affiliated Hospital, School of Medicine, Zhejiang University
Zhejiang Cancer Hospital
Zhejiang Provincial People's Hospital
First Affiliated Hospital of Zhejiang University
Sir Run Run Shaw Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Second Affiliated Hospital, School of Medicine, Zhejiang University

ClinicalTrials.gov Identifier:

NCT04380012

Other Study ID Numbers:

IR2019001210

First Posted:

May 8, 2020

Last Update Posted:

Jul 15, 2021

Last Verified:

Feb 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Second Affiliated Hospital, School of Medicine, Zhejiang University

HER2

Advanced Colorectal Cancer

Pyrotinib

Additional relevant MeSH terms:

Colorectal Neoplasms

Trastuzumab

Study Results

No Results Posted as of Jul 15, 2021