A Randomized, Multicenter, Open-Label, Phase III Study of Lapatinib in Combination With Trastuzumab Versus Lapatinib Monotherapy in Subjects With HER2-positive Metastatic Breast Cancer Whose Disease Has Progressed on Trastuzumab-Containing Regimens

GlaxoSmithKline1 site in 1 country296 target enrollmentNovember 2005

ConditionsNeoplasms, Breast

InterventionsLapatinib Trastuzumab

DrugsLapatinib

Overview

Phase: Phase 3
Intervention: Lapatinib
Conditions: Neoplasms, Breast
Sponsor: GlaxoSmithKline
Enrollment: 296
Locations: 1
Primary Endpoint: Progression-Free Survival (PFS)
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study will evaluate and compare the safety and efficacy of lapatinib in combination with trastuzumab versus lapatinib monotherapy in subjects with HER2-positive metastatic breast cancer.

Registry

clinicaltrials.gov

Start Date

November 2005

End Date

October 2010

Last Updated

10 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Signed informed consent.
•Female ≥18 years. Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (for example, intrauterine device \[IUD\], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product.
•Metastatic breast cancer, histologically/cytologically confirmed. If the disease is restricted to a solitary lesion, its neoplastic nature must be confirmed by cytology or histology.
•Subjects must have stage IV breast cancer whereby their disease has progressed in either the adjuvant or metastatic setting. Prior therapies must include, but are not limited to:
•Taxane-containing regimen for at least 4 cycles, or 2 cycles provided disease progression occurred while on taxane.
•Anthracycline-containing regimen for at least 4 cycles, or 2 cycles provided disease progression occurred while on anthracycline.
•Subjects must have documented progression following at least ONE trastuzumab plus cytotoxic chemotherapy or anti-hormonal regimen in the metastatic setting.
•Note: The most recent treatment must have contained trastuzumab, either alone or in combination with other therapy in the metastatic setting, and subjects must have progressed while on this regimen. Progression is defined as either new lesions or a ≥20% increase in the sum of longest diameter (LD) on the progression radiologic scan.
•Subjects must have archived tumor tissue available for testing.
•Documented amplification of the ErbB2 gene by fluorescence in situ hybridization (FISH) or documented overexpression of the ErbB2 protein by IHC in primary or metastatic tumor tissue. The IHC or FISH amplification may be documented by a local or central laboratory for randomization into the study. Subjects may be randomized on the basis of ErbB2 positivity by IHC 3+ overexpression or FISH amplification.

Exclusion Criteria

•Pregnant or lactating females.
•Prior therapy with an ErbB1 and/or ErbB2 inhibitor other than trastuzumab.
•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. However, 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.
•Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
•Active or uncontrolled infection.
•Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
•Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
•Known history or clinical evidence of leptomeningeal carcinomatosis.

Arms & Interventions

Arm 1: Lapatinib plus Trastuzumab

Lapatinib 1000mg once daily in combination with trastuzumab 4mg/kg loading dose followed by 2mg/kg weekly

Intervention: Lapatinib

Arm 1: Lapatinib plus Trastuzumab

Lapatinib 1000mg once daily in combination with trastuzumab 4mg/kg loading dose followed by 2mg/kg weekly

Intervention: Trastuzumab

Arm 2: Lapatinib

Lapatinib 1500mg once daily

Intervention: Lapatinib

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

Time Frame: Baseline to disease progression or death due to any cause or 30 days after last dose (up to 216 weeks)

PFS was defined as the time from randomization until the first documented sign of disease progression or death due to any cause.

Secondary Outcomes

Clinical Benefit Response (CBR)(Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks))
Overall Survival (OS)(Baseline to death or 30 days after last dose for the last participant (up to 216 weeks))
Duration of Response (DR)(Time from first documented evidence of CR or PR until the first documented sign of disease progression or death or 30 days after last dose (up to 216 weeks))
Overall Tumor Response (OR)(Baseline to disease progression or death or discontinuation from study or 30 days after last dose (up to 216 weeks))
Change From Baseline in Functional Assessment of Cancer Therapy-Breast (FACT-B) Scores at Week 4, Week 12, Week 16, Week 24, and Conclusion or Withdrawal From Study(Baseline, Week 4, Week 12, Week 16, Week 24, and conclusion or withdrawal from study (up to Week 108))
Time to Response (TTR)(Baseline until first documented evidence of CR or PR or 30 days after last dose (up to 216 weeks))
Time to Progression (TTP)(Baseline to disease progression or death or 30 days after last dose (up to 216 weeks))