Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors

Effect of Drug Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04960943
• Other study ID #: FUSCC-HER2-G
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2020
• Est. completion date: March 1, 2023

Study information

• Verified date: February 2021
• Source: Fudan University
• Contact: Xiaodong Xiaodong, phD
• Phone: 8621-64175590
• Email: xddr001[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 1, 2023
• Est. primary completion date: September 9, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Effect of Drug
• Gastrointestinal Neoplasms
• Gastrointestinal Tumor

Intervention

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.

Locations

Country	Name	City	State
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	overall survival(OS)	evaluated in the 24th month since the treatment began	24 months
Other	time to progression (TTP)	time to progression since the treatment began	24 months
Other	duration of response (DoR)	the time of duration of response	24 months
Other	disease control rate (DCR)	the proportion of patients who had a best response	24 months
Other	Safety and Tolerability	Number of Participants with treatment related Adverse Events as Assessed by CTCAE v5.0	24 months
Primary	Objective Response Rate (ORR)	evaluated in the 24th month since the treatment began	24 months
Secondary	Progression Free Survival (PFS)	evaluated in the 24th month since the treatment began	24 months