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

Primary Purpose

Colorectal Cancer

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

Pyrotinib

Pyrotinib in combination with trastuzumab

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring HER2, Advanced Colorectal Cancer, Pyrotinib

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

The Second Affiliated hospital of Zhejiang University School of MedicalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Single drug group

Dual-targeted drug group

Arm Description

Pyrotinib: 400 mg, po, qd, 21d for a treatment cycle

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

Outcomes

Primary Outcome Measures

Objective Response Rate

The proportion of patients with complete response or partial response according to RECIST v1.1.

Secondary Outcome Measures

Disease Control Rate

The proportion of patients with complete response, partial response or stable disease according to RECIST v1.1.

Progression-Free Survival

Time from the initiation of treatment to disease progression or any-cause death.

Overall Survival

Time from the initiation of treatment to any-cause death.

Duration of Response

Time from complete response or partial response to disease progression or any-cause death.

The Incidence of Adverse Events

Adverse Events and Serious Adverse Events were graded according to the NCI-CTCAE V5.0.

Full Information

NCT ID

NCT04380012

First Posted

February 4, 2020

Last Updated

July 13, 2021

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04380012

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2021

Overall Recruitment Status

Unknown status

Study Start Date

December 17, 2019 (Actual)

Primary Completion Date

December 17, 2021 (Anticipated)

Study Completion Date

June 17, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer

Keywords

HER2, Advanced Colorectal Cancer, Pyrotinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Single drug group

Arm Type

Experimental

Arm Description

Pyrotinib: 400 mg, po, qd, 21d for a treatment cycle

Arm Title

Dual-targeted drug group

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Pyrotinib

Intervention Description

Pyrotinib as interventions were used in patients with HER2-positive advanced colorectal cancer

Intervention Type

Drug

Intervention Name(s)

Pyrotinib in combination with trastuzumab

Intervention Description

Pyrotinib in combination with trastuzumab as interventions were used in patients with HER2-positive advanced colorectal cancer

Primary Outcome Measure Information:

Title

Objective Response Rate

Description

The proportion of patients with complete response or partial response according to RECIST v1.1.

Time Frame

Approximately 24 months

Secondary Outcome Measure Information:

Title

Disease Control Rate

Description

The proportion of patients with complete response, partial response or stable disease according to RECIST v1.1.

Time Frame

Approximately 24 months

Title

Progression-Free Survival

Description

Time from the initiation of treatment to disease progression or any-cause death.

Time Frame

Up to 2 years

Title

Overall Survival

Description

Time from the initiation of treatment to any-cause death.

Time Frame

Up to 2 years

Title

Duration of Response

Description

Time from complete response or partial response to disease progression or any-cause death.

Time Frame

Approximately 24 months

Title

The Incidence of Adverse Events

Description

Adverse Events and Serious Adverse Events were graded according to the NCI-CTCAE V5.0.

Time Frame

From the first drug administration to within 28 days for the last treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Ying Yuan, Doctor

Phone

+86 13858193601

yuany@z2hospital.com

First Name & Middle Initial & Last Name or Official Title & Degree

XianHua Fu, Doctor

Phone

+86 15258222675

fxh198501@163.com

Facility Information:

Facility Name

The Second Affiliated hospital of Zhejiang University School of Medical

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310009

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

XianHua Fu, Doctor

Phone

15858222675

fxh198501@163.com

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing Plan Description

The data were Shared with the sub-center, and the preliminary efficacy results were to be submitted to the tumor conference

Citations:

PubMed Identifier

36382603

Citation

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. 2023 Mar;114(3):1067-1074. doi: 10.1111/cas.15660. Epub 2022 Dec 5.

Results Reference

derived

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

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