Study Evaluating Pyrotinib/Pyrotinib in Combination With Docetaxel in Patients With HER2+ Advanced Gastric Cancer

HER2 Positive Gastric Cancer Clinical Trial

Official title:

A Phase I Study of Pyrotinib In Combination With Docetaxel In Patients With HER2 Positive Advanced Gastric Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02378389
• Other study ID #: BLTN-Id
• Status: Recruiting
• Phase: Phase 1
• First received: February 11, 2015
• Last updated: February 27, 2015
• Start date: September 2014
• Est. completion date: August 2017

Study information

• Verified date: February 2015
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: Qing Yang, MD
• Phone: 157 0515 5017
• Email: yangqing[@]hrs.com.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Pyrotinib is an oral tyrosine kinase inhibitor targeting both EGFR and HER-2 receptors. This study is designed to evaluate the safety and tolerability of Pyrotinib or Pyrotinib in combination with Docetaxel in patients with HER2 positive advanced gastric cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: August 2017
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Aged =18 and =70 years.

• ECOG performance status of 0 to 1.

• Life expectancy of more than 12 weeks.

• At least one measurable lesion exists.(RECIST 1.1).

• Histologically or cytologic confirmed HER2 positive advanced gastric cancer (including adenocarcinoma of esophageal-gastric junction), with clinical phase III/IV.

• No severe impairment of liver and kidney function, required laboratory values including following parameters:ANC:=1.5x109/L, Platelet count:=90x109/L, Hemoglobin:=9.0 g/dL, Total bilirubin:=1xULN, ALT and AST: =1.5xULN (for patients with liver metastases,ALT and AST:=5xULN), ALP:=2.5xULN, BUN and creatine:=1xULN, creatine clearance rate:=50 mL/min, LVEF:=50%, QTcF:<450 ms (male), <470 ms (female),INR:=1.5xULN, APTT:=1.5xULN.

• Signed informed consent.

For subjects treated by Pyrotinib only:

• Failed or intolerable of prior therapies.

For subjects treated by Pyrotinib with Docetaxel:

• Failed or intolerable of prior therapies, no previous treatment of taxane, no previous treatment of HER2 targeted inhibitors.

Exclusion Criteria:

• Subjects with third space fluid that can not be controled by drainage or other methods.

• Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption.

• Steroid treatment for more than 50 days, or in need of long-term use of steroids.

• Less than 4 weeks from the last radiotherapy,chemotherapy,surgery,hermone treatment,target therapy, or less than 6 weeks from the nitrosoureas or mitomycin chemotherapy.

• Less than 4 weeks from the last clinical trial or adverse events of previous trials (not including alopecia or asthenia).

• Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry.

• Subjects who can not interrupt using of the drugs causing QT prolongation during study.

• Subjects with intracranial lesions (by MRI or CT).

• Subjects suffered from other malignancies during last 5 years, not including cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma.

• Subjects with bone or skin as the only target lesion.

• Receiving any other antitumor therapy.

• Known history of hypersensitivity to any of the components or metabolites of the investigational drugs or to Tween-80.

• Subjects with clear tendency of gastointestinal bleeding. Including the following:

subjects with local active ulcer lesions and fecal occult blood (++) are excluded; subjects with less than 2 months from the last history of black stools or haematemesis are excluded; for subjects with fecal occult blood (+) and primary lesion not resected, endoscopy is required,if gastric ulcer is found and the principal investigator of the site consider possible occurence of gastointestinal bleeding, the subject should be excluded.

• Ongoing infection or peripheral neuropathy (determined by investigator).

• History of immunodeficiency, including HIV-positive, suffering from other acquired, congenital immunodeficiency disease, or history of organ transplantation.

• 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.

• Female patients who are pregnancy, lactation or women who are of childbearing potential tested positive in baseline pregnancy test or reluctant to take effective contraceptive measures throughout the trial period.

• Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study. Examples include, but are not limited to,hypertension, severe diabetes, or thyroid disease.

• Alcoholism, smoking (daily = 5 roots) and other bad habits.

• Known history of neurological or psychiatric disease, including epilepsy or dementia.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HER2 Positive Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Pyrotinib/Pyrotinib with Docetaxel
Pyrotinib oral daily, 240 mg, 320 mg, 400 mg.... Docetaxel i.v. once every 21 days.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital, Peking University	Beijing	Beijing
China	Cancer Hospital, Chinese Academy of Medical Sciences	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	Cancer center, Sun Yet-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The maximum-tolerated dose (MTD) of Pyrotinib and that of Pyrotinib with Docetaxel in patients with HER2 positive advanced gastric cancer	MTD will be defined as the maximum dose level at which no more than one subject out of three experience has a dose-limiting toxicity (DLT) upon completing one treatment cycle. DLT was defined as the certain AEs which were observed during the first cycle (D1-D21) of treatment	21 days	Yes
Secondary	Cmax of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer		12 months	Yes
Secondary	Tmax of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer		12 months	Yes
Secondary	T1/2 of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer		12 months	Yes
Secondary	AUCss of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer		12 months	Yes
Secondary	R of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer		12 months	Yes
Secondary	the number of participants with adverse event		12 months	Yes
Secondary	preliminary antitumor activity for the regimen		12 months	No