Overview

This trial is active, not recruiting.

Condition neoplasms, breast
Treatments lapatinib (gw572016), letrozole
Phase phase 3
Sponsor GlaxoSmithKline
Start date December 2003
End date June 2008
Trial size 1286 participants
Trial identifier NCT00073528, EGF30008, NCT00084968

Summary

This study will compare the efficacy and tolerability of GW572016 administered in combination with letrozole, versus letrozole and placebo, as treatment for hormone receptor-positive advanced or metastatic breast cancer.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Other)
Placebo plus letrozoleA daily dose of randomized therapy ) taken approximately at the same time each day.
letrozole Lapatinib (GW572016)
2.5 mg orally once a day
(Experimental)
GW572016 and letrozole A daily dose of randomized therapy ) taken approximately at the same time each day.
lapatinib (gw572016)
1500 mg orally once a day
letrozole Lapatinib (GW572016)
2.5 mg orally once a day

Primary Outcomes

Measure
Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Her3 as Assessed by the Investigator
time frame: From the date of randomization until the date of the first documented progression or date of death from any cause, whichever came first, assessed for up to 46 months
Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months

Secondary Outcomes

Measure
Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
PFS in Participants in the ITT Population as Assessed by the Investigator
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 46 months
Overall Survival in the HER2-Positive Population
time frame: From date of randomization until date of death due to any cause, assessed up to 46 months
Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator.
time frame: Up to 46 months
Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator.
time frame: Up to 46 months
Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population
time frame: Up to 46 months
Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator
time frame: Up to 46 months
Overall Survival in the ITT Population
time frame: From date of randomization until date of death due to any cause, assessed up to 46 months
Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With Evidence of Brain Metastases From the ITT Population
time frame: Up to 46 months
TTP for Participants From the ITT Population as Assessed by the Investigator
time frame: Up to 46 months
Number of Participants With the Indicated Adverse Events (AEs) Related to Study Treatment Reported in 10% or More Participants in Either Treatment Arm
time frame: Up to 46 months
Number of Participants With the Indicated Serious Adverse Events (SAEs) Related to Study Drug Reported by More Than One Participant in Either Treatment Arm
time frame: Up to 46 months
Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits
time frame: Day 1 (baseline) visit; Week 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, and 192 visits; conclusion/withdrawal visit
Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data
time frame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data
time frame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data
time frame: Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores
time frame: Up to 46 months
Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status
time frame: Up to 46 months
Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity
time frame: Up to 46 months
Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower
time frame: Up to 46 months
Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive
time frame: Up to 46 months
Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive
time frame: Up to 46 months
Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline
time frame: Baseline

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: - Signed informed consent; - Subjects must have histologically confirmed invasive breast cancer with stage IV disease at primary diagnosis or at relapse after curative-intent surgery [Singletary, 2002]; - Tumors that are ER+ and/or PgR+; - Subjects will be considered ER+ or PgR+ if any assay [cytochemical, immunochemical, immunohistochemistry (IHC), or radioimmunoassay] of primary or secondary tumor tissue is positive; - Post-menopausal female subjects =18 years of age; - ECOG Performance Status of 0 or 1; - Subjects must have archived tumor tissue available to compare tumor response with intra-tumoral expression of ErbB1 and ErbB2. Archived tumor tissue will also be used to confirm estrogen receptor (ER) and/or progesterone receptor (PgR) positivity. Results will not be used to determine subject eligibility for the study; - Adjuvant therapy with an aromatase inhibitor is allowed; however, treatment must have ended more than 1 year prior (>12 months) to the first dose of randomized therapy; - Adjuvant therapy with trastuzumab is allowed; however, treatment must have ended more than 1 year prior (>12 months) to the first dose of randomized therapy; - Subjects who received neo-adjuvant/adjuvant therapy and now present with newly relapsed advanced or metastatic disease are eligible; however, prior neo-adjuvant/adjuvant therapy is not required for study entry; 11. Subjects must have ended hormone replacement therapy (HRT) (e.g., conjugated estrogens tablets, USP, [Premarin]), at least 1 month (30 days) prior to receiving the first dose of randomized therapy; - Radiotherapy prior to initiation of randomized therapy is allowed to a limited area (e.g., palliative treatment for painful bone metastases), if it is not the sole site of disease. Subject must have completed treatment and recovered from all treatment related toxicities, in particular bone marrow suppression; - Able to swallow and retain oral medication; - Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram (or MUGA scan if an echocardiogram cannot be performed or is inconclusive); - Subjects must complete all screening assessments as outlined in the protocol; - Adequate organ function Exclusion Criteria: - Pre-menopausal, pregnant, or lactating; - Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for advanced or metastatic disease; - Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, is not permitted; - 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; - Subjects who have not recovered from toxicities related to prior adjuvant therapy (e.g., surgery, radiotherapy, chemotherapy, hormonal therapy, immunotherapy, biologic therapy, and investigational agents); - Subjects who have received anthracyclines in the neo-adjuvant and/or adjuvant setting, which exceeded the following doses: 360 mg/m2 of Doxorubicin, 720 mg/m2 of Epirubicin, and 72 mg/m2 of Mitoxantrone; - Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor, or the disease is considered by the investigator to be rapidly progressing or life threatening; - 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 of, or clinical evidence of, central nervous system (CNS) metastases or leptomeningeal carcinomatosis; - Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or tumor embolization) other than letrozole; - Concurrent treatment with an investigational agent or participation in another clinical trial; - Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy (GW572016 or placebo); - The subject has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to randomized therapy (GW572016 or placebo) or to excipients of randomized therapy (GW572016 or placebo); 18. Subject has known hypersensitivity to Femara or excipients of Femara

Additional Information

Official title A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study Comparing GW572016 and Letrozole Versus Letrozole in Subjects With Estrogen/Progesterone Receptor-Positive Advanced or Metastatic Breast Cancer
Trial information was received from ClinicalTrials.gov and was last updated in April 2015.
Information provided to ClinicalTrials.gov by GlaxoSmithKline.