Clinical trial NCT02535507: Efficacy and Safety of Pyrotinib in Patients With HER2 Mutation Advanced Non-Small Cell Lung Cancer
Official title: Single Arm Phase II Clinical Trial to Investigate the Efficacy and Safety of Pyrotinib as a Single Agent in HER2 Mutation Advanced Non-small Cell Lung Cancer Patients Who Failed to Previous at Least 2nd Line Treatments
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: pyrotinib
HER2
Non-small Cell Lung Cancer
Phase II
Lead sponsor: Tongji University
Sponsor class: OTHER
First posted: 2015-08-28
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Various driver gene mutations have been identified in lung cancer. Among them, human epidermal growth factor 2 (HER2) was identified in about approximately 2% of non-small cell lung cancers.Pyrotinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive advanced Non-small cell lung cancer.

Detailed description: This study is designed to evaluate the efficacy and safety of Pyrotinib in patients with HER2 positive advanced pre-treated Non-small cell lung cancer.

To observe objective response rate (ORR) of pyrotinib in HER2 positive NSCLC. To observe Progression free survival （PFS）. To assess the overall survival (OS). To assess side effects. To evaluate quality of life. To explore the relationship between biomarkers and the toxicity/efficacy of Pyrotinib.

Eligibility criteria: Inclusion Criteria:

* Aged ≥18 and ≤80 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 Non-small cell lung cancer who failed prior therapies.
* 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

* Signed informed consent.

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.
* Less than 4 weeks from the last radiotherapy,chemotherapy,target therapy
* 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.
* Receiving any other antitumor therapy.
* Known history of hypersensitivity to pyrotinib or any of it components. Ongoing infection (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.
* Known history of neurological or psychiatric disease, including epilepsy or dementia.

Primary outcomes:
measure: Objective Response Rate
timeFrame: tumor assessment every 6-8 weeks after the initiation of pyrotinib, up to 24 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: 24 months
Other outcomes:
measure: overall survival
timeFrame: 24 months
measure: Safety and Tolerability
timeFrame: 24 months
measure: quality of life (measured by questionnaire)
timeFrame: 24 months
Locations:
city: Shanghai
country: China
facility: Department of Oncology, Shanghai pulmonary hospital
Study officials:
affiliation: Shanghai Pulmonary Hospital, Tongji University
name: Caicun Zhou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wang Y, Jiang T, Qin Z, Jiang J, Wang Q, Yang S, Rivard C, Gao G, Ng TL, Tu MM, Yu H, Ji H, Zhou C, Ren S, Zhang J, Bunn P, Doebele RC, Camidge DR, Hirsch FR. HER2 exon 20 insertions in non-small-cell lung cancer are sensitive to the irreversible pan-HER receptor tyrosine kinase inhibitor pyrotinib. Ann Oncol. 2019 Mar 1;30(3):447-455. doi: 10.1093/annonc/mdy542.