Efficacy and Safety of Pyrotinib in Patients With HER2 Mutation Advanced Non-Small Cell Lung Cancer

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

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.

Study Overview

• Status: Unknown
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Pyrotinib

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 200433
    • Recruiting
    • Department of Oncology, Shanghai pulmonary hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pyrotinib treatment arm; pyrotinib treatment arm	Drug: Pyrotinib; Drug: Pyrotinib pyrotinib, single agent, 400mg p.o once daily until disease progressed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	To evaluate objective response rate 6-8 weeks after the initiation of pyrotinib	tumor assessment every 6-8 weeks after the initiation of pyrotinib, up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	PFS is evaluated in 24 months since the treatment began	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	evaluated in the 24th month since the treatment began	24 months
Safety and Tolerability	Number of Participants with treatment related Adverse Events as Assessed by CTCAE v4.0	24 months
quality of life (measured by questionnaire)	Change from baseline in Pain on the 11 point short pain scale (SPS-11)	24 months

Collaborators and Investigators

• Sponsor: Tongji University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: August 25, 2015
• First Submitted That Met QC Criteria: August 27, 2015
• First Posted (Estimate): August 28, 2015

Study Record Updates

• Last Update Posted (Estimate): August 28, 2015
• Last Update Submitted That Met QC Criteria: August 27, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: HER2; Phase II; Non-small Cell Lung Cancer; pyrotinib
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: FK1406