Safety and Clinical Activity of Lapatinib in Patients With HER2-positive Refractory Advanced Cancer

Safety and Clinical Activity of Lapatinib in Patients With HER2-positive Refractory Advanced Cancer: A Phase II Single Arm Prospective Study

Although anti-HER2 (human epidermal growth factor receptor 2) therapy is currently approved for breast, gastric, and gastroesophageal cancers overexpressing the HER2 protein or amplified for the HER2 gene, HER2 aberrations (gene amplification, gene mutations, and protein overexpression) are reported in other diverse malignancies. Indeed, about 1-37% of tumors of the following types harbor HER2 aberrations: bladder, cervix, colon, endometrium, germ cell, glioblastoma, head and neck, liver, lung, ovarian, pancreas, and salivary duct.

Lapatinib is an orally active, reversible, small molecule TKI that potently inhibits both ErbB1 and ErbB2 tyrosine kinase activity. Data suggest that a dual ErbB1 and ErbB2 inhibitor may provide improved therapeutic benefit compared with inhibitors that target only one or the other receptor.

Therefore, this phase 2 study is designed to evaluated the activity of lapatinib in patients with HER2-positive refractory cancer.

Study Overview

• Status: Completed
• Conditions: HER2-positive Refractory Advanced Cancer
• Intervention / Treatment: Drug: Lapatinib

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 19
• Written informed consent
• ECOG 0-2,
• Histologically confirmed HER2-positive Refractory solid tumor(IHC 3+ alone, or IHC 2+ with FISH amplification) and/or specific sensitivity to Lapatinib by Avatar scan that has progressed following standard therapy or that has not responded to standard therapy or for which there is no standard therapy.
• The presence of measurable disease as defined by the Response (Evaluation Criteria in Solid Tumors (RECIST) version 1.1)
• Adequate organ function

Exclusion Criteria:

• Uncontrolled symptomatic brain metastasis,Uncontrolled active infection
• Uncontrolled systemic illness (DM, CHF, unstable angina, hypertension or arrhythmia)
• Prolonged QT interval in ECG (QTc >450 msec)
• Pregnant, lactating women
• Prior treatment with lapatinib,Malabsorption syndrome, any disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, or persons unable to swallow oral medication
• Prior history of malignancy within 5 years from study entry except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, well-treated thyroid cancer

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: single arm; Patients will be treated with oral lapatinib 1250mg once daily for 21 days.	Drug: Lapatinib; Patients will be treated with oral lapatinib 1250mg once daily for 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall response rate	4 weeks after treatment of lapatinib

Collaborators and Investigators

• Sponsor: Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2014
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): August 21, 2016

Study Registration Dates

• First Submitted: January 15, 2015
• First Submitted That Met QC Criteria: January 20, 2015
• First Posted (Estimate): January 21, 2015

Study Record Updates

• Last Update Posted (Actual): February 17, 2017
• Last Update Submitted That Met QC Criteria: February 16, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Lapatinib
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lapatinib
• Other Study ID Numbers: 2014-10-028