Phase II Clinical Study of Lapatinib (GW572016) in Patients With ErbB2 Over - Expressing Advanced or Metastatic Breast Cancer

GlaxoSmithKline1 site62 target enrollmentNovember 28, 2005

ConditionsNeoplasms, Breast

Interventionslapatinib

Drugslapatinib

Overview

Phase: Phase 2
Intervention: lapatinib
Conditions: Neoplasms, Breast
Sponsor: GlaxoSmithKline
Enrollment: 62
Locations: 1
Primary Endpoint: Overall Tumor Response
Status: Completed
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study (EGF104911) is designed to evaluate the efficacy and safety of lapatinib in patients with advanced or metastatic breast cancer. Eligible subjects must have ErbB2 overexpressing tumors and are refractory to treatment with anthracycline, taxanes and trastuzumab containing regimens. The study data obtained from EGF104911 will be combined with the data from EGF100642 and integrated analysis will be carried out in order to enhance the credibility of the study results.

Registry

clinicaltrials.gov

Start Date

November 28, 2005

End Date

April 1, 2009

Last Updated

7 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•A subject will be considered eligible for inclusion in this study only if all of the following criteria apply:
•Life expectancy of ≥16 weeks from the start of lapatinib therapy;
•Signed informed consent obtained from the patient;
•Subjects must have histologically confirmed breast cancer with advanced (Stage IIIb, IIIc with T4 lesion) or metastatic disease (including recurrent patients);
•Subjects must meet the following criteria regarding prior therapy:
•Anthracyclines, taxanes:
•If anthracycline- and taxane-containing regimens are administered sequentially;
•Subjects should have been provided with at least 2 cycles each and at least 4 cycles in total.
•If anthracycline- and taxane-containing regimen are administered concurrently;
•Subjects should have been provided with at least 4 cycles in total. or

Exclusion Criteria

•A subject will not be eligible for inclusion in this study if any of the following criteria apply:
•Pregnant or lactating females;
•Malabsorption Syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with ulcerative colitis are also excluded;
•History of other malignancy. Subjects who have been disease free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
•Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety \* \[\* ≥Grade 3 (according to NCI-CTCAE Version 3.0), as a general rule\];
•Active or uncontrolled infection;
•Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
•Known history of or clinical evidence of leptomeningeal carcinomatosis;
•Participated in a clinical study within the past 28 days of the first dose of lapatinib;
•Prior therapy with an ErbB1inhibitor (e.g., gefinitib) and/or ErbB2 inhibitor other than trastuzumab;

Arms & Interventions

Lapatinb

Lapatinib 1500mg QD

Intervention: lapatinib

Outcomes

Primary Outcomes

Overall Tumor Response

Time Frame: Baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.

Tumor response was measured as the number of participants achieving either a complete response (CR; disappearance of all target lesions) or partial response (PR; 30% decrease in the sum of the longest diameter of target lesions) among all participants who received study treatment. Tumor response was evaluated as the best response in accordance with response evaluation criteria in solid tumors (RECIST). Progressive disease: a 20% increase in the sum of the longest diameter of target lesions. Stable disease: small changes that do not meet the above-mentioned criteria.

Secondary Outcomes

Duration of Response(First noted efficacy to disease progression; baseline and followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression is noted.)
Mean Phosphorylated 58 kDa Serine/Threonine Protein Kinase (p-AKT) H Score for All Participants(Tumor samples taken at baseline)
Mean p-BAD H Score for All Participants(Tumor samples taken at baseline)
Mean Bcl-2 H Score for All Participants(Tumor samples taken at baseline)
Time to Progression(Baseline to disease progression or death; baseline and then followed every 4 weeks until disease progression or death. If treatment was terminated due to adverse events, then followed every 12 weeks until disease progression or death.)
Time to Response(Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse event, then followed every 12 weeks until DP or death.)
6-month Progression Free Survival(Baseline to Month 6 (Week 24))
Clinical Benefit(Time at which all participants had been followed for at least 24 weeks; baseline and then followed every 4 weeks until disease progression (DP) or death. If treatment was terminated due to adverse events, then followed every 12 weeks until DP or death.)
4-month Progression Free Survival(Baseline to Month 4 (Week 16))
Overall Survival(Start of dosing to death; baseline and then followed every 4 weeks until death while on treatment. If alive at time of treatment termination, then followed every 12 weeks until death.)
Mean Insulin-like Growth Factor 1 Receptor (IGF1R) H Score for All Participants(Tumor samples taken at baseline)
Mean Survivin H Score for All Participants(Tumor samples taken at baseline)
Mean Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) H Score for All Participants(Tumor samples taken at baseline)
Mean Epidermal Growth Factor Receptor 3 (ErbB3) H Score for All Participants(Tumor samples taken at baseline)
Mean Epidermal Growth Factor Receptor 4 (ErbB4) H Score for All Participants(Tumor samples taken at baseline)
Mean Phosphorylated Extracellular Signal-regulated Kinase (p-ERK) H Score for All Participants(Tumor samples taken at baseline)
Mean Heregulin H Score for All Participants(Tumor samples taken at baseline)