Clinical trial NCT04960943: Efficacy and Safety of Pyrotinib in HER2 Positive Gastrointestinal Tumors
Official title: Efficacy and Safety of Pyrotinib in Patients With HER2 Positive Refractory or Metastatic Gastrointestinal Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Gastrointestinal Tumor
Effect of Drug
Keywords: pyrotnib, HER2, Gastrointestinal Tumor, Phase II
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2021-07-14
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 24 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 24 months
Other outcomes:
measure: overall survival(OS)
timeFrame: 24 months
measure: time to progression (TTP)
timeFrame: 24 months
measure: duration of response (DoR)
timeFrame: 24 months
measure: disease control rate (DCR)
timeFrame: 24 months
measure: Safety and Tolerability
timeFrame: 24 months
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Fudan University
name: Xiaodong Zhu, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.