Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors

Efficacy and Safety of Pyrotinib in Patients With HER2 Positive Refractory or Metastatic Gastrointestinal Tumors

Targeting human epidermal factor receptor 2 (HER2) therapy have shown the anti-tumor efficacy in patients with HER2-positive gastrointestinal tumors. Pyrotinib is an irreversible small-molecule receptor tyrosine kinase inhibitor targeting both epidermal growth factor receptor (EGFR) and HER2. This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors.

Study Overview

• Status: Recruiting
• Conditions: Effect of Drug; Gastrointestinal Tumor
• Intervention / Treatment: Drug: Pyrotinib with or without trastuzumab

Detailed Description

This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive gastrointestinal tumors. Three cohorts were designed for this trial. Cohort 1: patients with gastric cancer or esophageal adenocarcinoma receiving paclitaxel combined with pyrotinib for second-line therapy; Cohort 2: patients with gastric cancer or esophageal adenocarcinoma receiving pyrotinib monotherapy for third-line or posterior line therapy; Cohort 3: patients with colorectal cancer receiving pyrotinib combined with/without trastuzumab for third-line or posterior line therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaodong Xiaodong, phD; Phone Number: 8621-64175590; Email: xddr001@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Wenhua Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Aged ≥18
2. ECOG performance status of 0 to 1.
3. Life expectancy of more than 12 weeks.
4. At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed HER2 positive gastrointestinal tumors who failed prior therapies.

5. Required laboratory values including following parameters:

   ANC: ≥ 1.5 x 10^9/L, Platelet count: ≥ 80 x 10^9/L, Hemoglobin: ≥ 90 g/L, Total bilirubin: ≤ 1.5 x upper limit of normal, ULN, ALT and AST: ≤ 1.5 x ULN, BUN and creatine clearance rate: ≥ 50 mL/min LVEF: ≥ 50% QTcF: < 470 ms

6. Signed informed consent.

Exclusion Criteria:

1. Subjects with third space fluid that can not be controled by drainage or other methods.
2. Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption.
3. Less than 4 weeks from the last radiotherapy, chemotherapy, target therapy
4. Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. Subjects who can not interrupt the using of the drugs that may cause QT prolongation during study.
5. Receiving any other antitumor therapy.
6. Known history of hypersensitivity to pyrotinib or any of it components. Ongoing infection (determined by investigator).
7. History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.
8. Subjects had any heart disease, including: (1) angina; (2) requiring medication or clinically significant arrhythmia; (3) myocardial infarction; (4) heart failure; (5) Any heart diseases judged by investigator as unsuitable to participate in the trial.
9. Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test.
10. Known history of neurological or psychiatric disease, including epilepsy or dementia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pyrotinib; Pyrotinib with or without paclitaxel/trastuzumab treatment

Drug: Pyrotinib with or without trastuzumab; After enrollment, patients of all the three cohorts were given 400 mg/d oral pyrotinib continuously, every 21 days as a cycle; Cohort 1 and 2 : Patients with gastric cancer or esophageal adenocarcinoma were combined with paclitaxel 80 mg/m2, intravenously, once on the first and eighth day. Cohort 3: Patients with colorectal cancer were given trastuzumab at an initial load dose of 8 mg/kg followed by 6 mg/kg every 3 weeks.; Other Names: pyrotinib with other drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	evaluated in the 24th month since the treatment began	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	evaluated in the 24th month since the treatment began	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival(OS)	evaluated in the 24th month since the treatment began	24 months
time to progression (TTP)	time to progression since the treatment began	24 months
duration of response (DoR)	the time of duration of response	24 months
disease control rate (DCR)	the proportion of patients who had a best response	24 months
Safety and Tolerability	Number of Participants with treatment related Adverse Events as Assessed by CTCAE v5.0	24 months

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Xiaodong Zhu, phD, Fudan University

Publications and helpful links

General Publications

• Chang J, Xu M, Wang C, Huang D, Zhang Z, Chen Z, Zhu X, Li W. Dual HER2 Targeted Therapy With Pyrotinib and Trastuzumab in Refractory HER2 Positive Metastatic Colorectal Cancer: A Result From HER2-FUSCC-G Study. Clin Colorectal Cancer. 2022 Dec;21(4):347-353. doi: 10.1016/j.clcc.2022.07.003. Epub 2022 Jul 16.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Anticipated): September 9, 2022
• Study Completion (Anticipated): March 1, 2023

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: July 9, 2021
• First Posted (Actual): July 14, 2021

Study Record Updates

• Last Update Posted (Actual): July 14, 2021
• Last Update Submitted That Met QC Criteria: July 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: pyrotnib, HER2, Gastrointestinal Tumor, Phase II
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: FUSCC-HER2-G

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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