The Safety and Effects of Gefitinib in Triple-negative,EGFR Positive Metastatic Breast Cancer

Phase Ⅱ Study of Gefitinib in Triple-negative,EGFR Positive Metastatic Breast Cancer

Breast cancer is a heterogeneous disease and can be classified into several distinctive subgroups. Triple-negative breast cancer(TNBC) is defined by lack of estrogen(ER), progesterone(PR) immunoreactivity and lack of human epidermal receptor-2(HER2) overexpression. TNBC comprises around 15% of all breast cancer and is characterized by its aggressive clinical behavior and insensitivity toward available targeted treatment strategies such as endocrine and anti-HER2 therapies.Although TNBC is sensitive to chemotherapy,early relapse with metastatic disease is common and the prognosis is poor. Development Of novel treatment strategies is,therefore,needed and the study of other potential targets in TNBC,like tyrosine kinase receptors,is a topic of interest.

Epidermal Growth Factor Receptor(EGFR) is a transmembrane receptor tyrosine kinase that encoded by cell erythroblastosis virus oncogene B1(C-erbB1) and belongs to the HER/Erythroblastosis virus oncogene B(ErbB) family. By several signal pathways,EGFR regulates cell proliferation, differentiation, apoptosis, invasion,and angiogenesis,and serves as a poor prognostic factor.EGFR is overexpressed in a variety of malignancies including TNBC.Gene expression profiling and immunohistochemical studies have indicated that 40 to 60% of TNBCs exhibit EGFR expression and gene amplification was found in 18% of this subgroup,but EGFR mutation was rare in TNBC.

By far,the role of gefitinib, an EGFR tyrosine kinase inhibitor(TKI),in the metastatic TNBC has not been identified. Most clinical trials about EGFR TKIs in the breast cancer have one or more limitations including:1) the study population had received heavily pretreatment; 2)the enrolled patients included several subgroups of breast cancer; 3)the expression of EGFR was not clear in the enrolled patients.

Here, the investigators launch a prospective clinical trial, and about 50 patients with triple-negative,EGFR positive metastatic breast cancer that have received at least second line therapy will be enrolled. these patients will be treated with gefitinib, the toxicity and effects of gefitinib will be recorded prospectively to evaluate the role of gefitinib in the metastatic TNBC.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: gefitinib

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ≥18 years of age
• ≥1 measurable or assessable lesion
• Eastern Cooperative Oncology Group(ECOG)performance status of 0-2
• adequate renal,hepatic and hematological function
• a life expectancy of >12 weeks
• histologically proven EGFR positive metastatic TNBC

Exclusion Criteria:

• brain metastasis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gefitinib; gefitinib tablet 250mg/day by mouth until disease progression	Drug: gefitinib; Other Names: IRRESA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical benefit rate	The primary end point is objective clinical benefit rate defined as objective response or stable disease for≥24wk	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progress-free survival（PFS）	Progress-free survival（PFS）is defined as the time from start of treatment to progression or death.	every 4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Toxicity is assessed twice weekly and adverse effects(AEs) are classified according to the National Cancer Institute Common Toxicity Criteria(NCI-CTC).	twice weekly

Collaborators and Investigators

• Sponsor: Jiangmen Central Hospital
• Investigators: Principal Investigator: gengsheng yu, Department of oncology, Jiangmen central hospital, Jiangmen, China

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): April 1, 2015
• Study Completion (Anticipated): October 1, 2015

Study Registration Dates

• First Submitted: November 19, 2012
• First Submitted That Met QC Criteria: November 19, 2012
• First Posted (Estimate): November 22, 2012

Study Record Updates

• Last Update Posted (Estimate): December 3, 2012
• Last Update Submitted That Met QC Criteria: November 30, 2012
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Keywords: Triple-negative breast cancer; Gefitinib; Epidermal growth factor receptor
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: 20120314