Clinical trial NCT02378389: Study Evaluating Pyrotinib/Pyrotinib in Combination With Docetaxel in Patients With HER2+ Advanced Gastric Cancer
Official title: A Phase I Study of Pyrotinib In Combination With Docetaxel In Patients With HER2 Positive Advanced Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: HER2 Positive Gastric Cancer
Lead sponsor: Jiangsu HengRui Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-03-04
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: The maximum-tolerated dose (MTD) of Pyrotinib and that of Pyrotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 21 days
Secondary outcomes:
measure: Cmax of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 12 months
measure: Tmax of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 12 months
measure: T1/2 of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 12 months
measure: AUCss of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 12 months
measure: R of Pyrotinib and Pytotinib with Docetaxel in patients with HER2 positive advanced gastric cancer
timeFrame: 12 months
measure: the number of participants with adverse event
timeFrame: 12 months
measure: preliminary antitumor activity for the regimen
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital, Peking University
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
city: Guangzhou
country: China
facility: Cancer center, Sun Yet-sen University
state: Guangdong
Study officials:
References:
citation: Chen Z, Xu Y, Gong J, Kou F, Zhang M, Tian T, Zhang X, Zhang C, Li J, Li Z, Lai Y, Zou J, Zhu X, Gao J, Shen L. Pyrotinib combined with CDK4/6 inhibitor in HER2-positive metastatic gastric cancer: A promising strategy from AVATAR mouse to patients. Clin Transl Med. 2020 Aug;10(4):e148. doi: 10.1002/ctm2.148.