Overview

This trial is active, not recruiting.

Condition metastases, brain
Treatments capecitabine, lapatinib, trastuzumab
Phase phase 3
Targets HER2, AKT, CDK, EGFR, ERK
Sponsor GlaxoSmithKline
Start date April 2009
End date June 2012
Trial size 546 participants
Trial identifier NCT00820222, 111438

Summary

This open label study is designed to evaluate Lapatinib effect on incidence of brain metastases in ErbB2 (HER2) positive metastatic breast cancer patients exposed to prior taxanes or anthracyclines.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Lapatinib 1250 mg once daily and capecitabine 2000mg/m2/day, days 1-14, every 21 days
capecitabine
oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle
lapatinib
oral medication; daily dose taken once a day
(Active Comparator)
trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions, and capecitabine 2500mg/m2/day, days 1-14, every 21 days
capecitabine
oral medication; daily dose divided into morning and evening dose and taken for 14 days of 21 day cycle
trastuzumab
infusion therapy; loading dose of 8mg/kg, followed by 6mg/kg given every 3 weeks

Primary Outcomes

Measure
Number of Participants With Central Nervous System (CNS) Metastases (as Assessed by Independent Review) as the Site of First Relapse
time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months)

Secondary Outcomes

Measure
Progression Free Survival (PFS), as Assessed by the Investigator
time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months)
Time to First CNS Progression, Defined as the Time From Randomization Until the Date of Documented CNS Progression as the First Site of Relapse
time frame: From randomization until the date of documented CNS progression (average of 10 months)
Overall Survival
time frame: From randomization until death due to any cause (average of 10 months)
Number of Participants With Overall Response (OR), as Assessed by the Investigator
time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months)
Number of Participants With Clinical Benefit (CB)
time frame: From randomization until disease progression, death, or discontinuation from the study (average of 10 months)
Duration of Response
time frame: From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months)
Number of Participants With CNS Progression at Any Time
time frame: From the time of randomization until death due to any cause (average of 10 months)
Number of Participants With the Indicated Grade 3 or Grade 4 Adverse Events (AEs) Occurring in >=2 Participants in Either Treatment Arm
time frame: From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months)
Number of Participants With Qualitative and Quantitative Toxicities
time frame: From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months)
Number of Participants Expressing Glucocorticoid Receptor, Phosphatase and Tensin Homolog (PTEN), Phosphatidylinositide 3-kinase (PI3K)/AKT, Protein 53 (P53), Insulin-like Growth Factor-1 (IGF-1), and Genes Involved in Cell Cycle Regulation
time frame: Baseline

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Females at least 18 years old; - ECOG Performance Status 0-2; - Histologically or cytologically confirmed HER2-positive invasive breast cancer, with Stage IV disease; - Prior treatment with taxanes or anthracyclines is required; - Prior treatment with other chemotherapeutic agents, trastuzumab, endocrine and radiation therapy is permitted; - Baseline LVEF ≥ 50% and not lower than the institutional lower limit of normal; - Concurrent treatment with bisphosphonates is permitted, however treatment must be initiated prior to the first dose of study therapy; - Able to swallow and retain oral medications; - Women with potential to have children must be willing to practice acceptable methods of birth control during the study; - Normal organ and marrow function. Exclusion Criteria: - History and/or current evidence of CNS metastases. Baseline MRI scan by Independent Reviewer to confirm no brain mets; - Concurrent treatment with an investigational agent or participation in another treatment clinical trial; - Prior therapy with lapatinib or an ErbB2 inhibitor other than trastuzumab (including but not limited to trastuzumab-DM1 and neratinib) and capecitabine; - Known DPD deficiency; - Concurrent chemotherapy, radiation therapy, immunotherapy, biologic therapy, or hormonal therapy for treatment of cancer; - History of allergic reactions attributed to compounds chemically related to lapatinib (quinazolines), capecitabine, fluorouracil or any excipients; - Concomitant use of CYP3A4 inhibitors or inducers; - Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel; - History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents, or other contraindication to gadolinium contrast and other known contraindication to MRI; - Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical or psychiatric disorder that would interfere with the patient's safety or compliance to study procedures; - have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease); - Any on-going toxicity from prior anti cancer therapy except alopecia; - Active cardiac disease; - Uncontrolled infection; - History of other malignancy, unless curatively treated with no evidence of disease for at least 5 years, subjects with adequately treated DCIS or LCIS, adequately treated non-melanoma skin cancer or curatively treated in-situ cancer of the cervix are eligible; - Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of protocol treatment; - Pregnant or lactating females.

Additional Information

Official title A Randomized, Multicentre, Open-Label, Phase III Study of Lapatinib Plus Capecitabine Versus Trastuzumab Plus Capecitabine in Patients With Anthracycline- or Taxane-Exposed ErbB2-Positive Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in February 2014.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.