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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00073528




Trial ID
NCT00073528
Ethics application status
Date submitted
24/11/2003
Date registered
25/11/2003
Date last updated
18/05/2018

Titles & IDs
Public title
Study Comparing GW572016 And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
Scientific 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
Secondary ID [1] 0 0
EGF30008
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms, Breast 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lapatinib (GW572016)
Treatment: Drugs - Letrozole

Other: Placebo plus letrozole - Placebo plus letrozoleA daily dose of randomized therapy ) taken approximately at the same time each day.

Experimental: lapatinib plus letrozole - GW572016 and letrozole A daily dose of randomized therapy ) taken approximately at the same time each day.


Treatment: Drugs: Lapatinib (GW572016)
1500 mg orally once a day

Treatment: Drugs: Letrozole
2.5 mg orally once a day

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Her3 as Assessed by the Investigator - PFS is defined as the time from randomization until the earliest date of disease progression (PD) or death due to any cause, if sooner. The date of documented PD is defined as the date of radiological PD as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0), PD is defined as a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Timepoint [1] 0 0
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
Primary outcome [2] 0 0
Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator - PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Timepoint [2] 0 0
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 outcome [1] 0 0
Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator - PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Timepoint [1] 0 0
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 outcome [2] 0 0
PFS in Participants in the ITT Population as Assessed by the Investigator - PFS is defined as the time from randomization until the earliest date of disease progression or death due to any cause, if sooner. The date of documented disease progression is defined as the date of radiological disease progression as assessed by the investigator based on imaging data and also by the clinical assessment of symptomatic progression. Per RECIST 1.0, disease progression is defined as a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions.
Timepoint [2] 0 0
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 outcome [3] 0 0
Overall Survival in the HER2-Positive Population - Overall survival was defined as the time from randomization until death due to any cause.
Timepoint [3] 0 0
From date of randomization until date of death due to any cause, assessed up to 46 months
Secondary outcome [4] 0 0
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 - OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.
Timepoint [4] 0 0
Up to 46 months
Secondary outcome [5] 0 0
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 - Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT to the randomization date.
Timepoint [5] 0 0
Up to 46 months
Secondary outcome [6] 0 0
Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator - CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement.
Timepoint [6] 0 0
Up to 46 months
Secondary outcome [7] 0 0
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. - CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions.
Timepoint [7] 0 0
Up to 46 months
Secondary outcome [8] 0 0
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. - CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum LD since the baseline measurement. The best overall response is defined as the best response recorded from the start of treatment until disease progression/recurrence. PD: presence of target lesions, non-target lesions, and/or new lesions.
Timepoint [8] 0 0
Up to 46 months
Secondary outcome [9] 0 0
Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator - Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans.
Timepoint [9] 0 0
Up to 46 months
Secondary outcome [10] 0 0
Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator - Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans.
Timepoint [10] 0 0
Up to 46 months
Secondary outcome [11] 0 0
Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population - The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another.
Timepoint [11] 0 0
Up to 46 months
Secondary outcome [12] 0 0
Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator - TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator.
Timepoint [12] 0 0
Up to 46 months
Secondary outcome [13] 0 0
Overall Survival in the ITT Population - Overall survival was defined as the time from randomization until death due to any cause.
Timepoint [13] 0 0
From date of randomization until date of death due to any cause, assessed up to 46 months
Secondary outcome [14] 0 0
Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator - OR is defined as the percentage of participants achieving either a confirmed complete response (CR) or partial response (PR). Response was assessed via Response Evaluation criteria in Solid Tumors (RECIST). The percentage of participants with response was calculated by using the formula: 100 * (number of participants with CR + number of participants with PR)/total number of participants. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD.
Timepoint [14] 0 0
Up to 46 months
Secondary outcome [15] 0 0
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 - Participants were stratified based on site of disease at screening (SDS) (soft tissue or visceral or bone-only disease) and prior adjuvant endocrine therapy (PAET) (discontinuation interval [DI] =>6 months or DI <6 months). OR is defined as the number of participants achieving either a confirmed CR or PR. Response was assessed via RECIST. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. DI is defined as the time period from stopping the PEAT and the randomization date.
Timepoint [15] 0 0
Up to 46 months
Secondary outcome [16] 0 0
Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator - CB is defined as the percentage of participants with evidence of confirmed CR, PR, or stable disease (SD) for at least 6 months. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the baseline measurement.
Timepoint [16] 0 0
Up to 46 months
Secondary outcome [17] 0 0
Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator - Time to response is defined as the time from randomization until the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sume of the LD of target lesions, taking as reference the baseline sum LD) (whichever status was recorded first). The assessments of CR or PR required confirmation using bone scans.
Timepoint [17] 0 0
Up to 46 months
Secondary outcome [18] 0 0
Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator - Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of target lesions, taking as a reference the baseline sum LD) until the first documented sign of disease progression or death due to any cause. The assessments of CR or PR required confirmation using bone scans.
Timepoint [18] 0 0
Up to 46 months
Secondary outcome [19] 0 0
Number of Participants With Evidence of Brain Metastases From the ITT Population - The confirmation criteria for the evidence of brain metastases was the incidence of lesions occurring within any part of the central nervous system (CNS) as evidenced by radiological scans. Metastases are defined as the spread of cancer from one part of the body to another.
Timepoint [19] 0 0
Up to 46 months
Secondary outcome [20] 0 0
TTP for Participants From the ITT Population as Assessed by the Investigator - TTP is defined as the interval between the date of randomization and the earliest date of disease progression or death due to breast cancer. Disease progression was based on the assessments by the Investigator.
Timepoint [20] 0 0
Up to 46 months
Secondary outcome [21] 0 0
Number of Participants With the Indicated Adverse Events (AEs) Related to Study Treatment Reported in 10% or More Participants in Either Treatment Arm - An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was possibly or probably related to study treatment.
Timepoint [21] 0 0
Up to 46 months
Secondary outcome [22] 0 0
Number of Participants With the Indicated Serious Adverse Events (SAEs) Related to Study Drug Reported by More Than One Participant in Either Treatment Arm - An SAE is any event occurring at any dose that results in any of the following: death, a life-threatening adverse drug experience (ADE; at immediate risk of death from the experience as it occurred), inpatient hospitalization/prolongation of existing hospitalization, a persistent/significant disability/incapacity, or a congenital anomaly/birth defect. Medical events that may not result in death, be life threatening, or require hospitalization may be considered to be a serious ADEs when based upon appropriate medical judgment. Relatedness was based on the Investigator's medical judgement.
Timepoint [22] 0 0
Up to 46 months
Secondary outcome [23] 0 0
Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits - Quality of Life (QOL) was assessed using the FACT-B questionnaire, which was a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales (each ranging from 0 [not at all] to 4 [very much]) indicate a higher QOL. The score is transformed for FACT-B and results in a total score ranging from 0 to 144. Complete: completing at least 1 question from FACT-B.
Timepoint [23] 0 0
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
Secondary outcome [24] 0 0
Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data - Quality of Life (QOL) was assessed using the FACT-B questionnaire, which is a 37-item (27 general and 10 breast cancer-specific questions) self-reporting instrument consisting of 5 dimensions: physical-, social/family-, emotional-, functional-well being, and a breast cancer subscale. Higher scores on the FACT-B scales indicate a higher QOL; each ranging from 0 (not at all) to 4 (very much). The score is transformed for FACT-B and results in a total score ranging from 0 to 144. The FACT-B is designed to measure multidimensional QOL in participants with breast cancer.
Timepoint [24] 0 0
Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Secondary outcome [25] 0 0
Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data - FACT-G is a subscale of the FACT-B QOL questionnaire and consists of 27 questions grouped into 4 domains that measure a participant's physical, functional, social and family, and emotional well-being. FACT-G is assessed on a five-point Likert-type scale, with scores ranging from 0 to 4 (0=not at all, 1=a little bit, 2=somewhat, 3=quite a bit, 4=very much). The total score is calculated as the sum of the item scores on the subscale; the total ranges from 0 to 108, with higher score indicating a better quality of life.
Timepoint [25] 0 0
Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Secondary outcome [26] 0 0
Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data - The TOI score is the sum of the physical well-being, functional well-being, and breast cancer unweighted subscale scores. The total TOI score ranges from 0 to 92, with higher scores representing a better quality of life.
Timepoint [26] 0 0
Week 12, 24, 36, and 48 visits; conclusion/withdrawal visit
Secondary outcome [27] 0 0
Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores - A minimally important difference (MID) is the smallest difference in a score for a measure of QOL that corresponds to a difference in function or clinical course. Responders are defined as participants with an MID => 8 for the FACT-B score, and an MID =>6 for the FACT-G and TOI scores.
Timepoint [27] 0 0
Up to 46 months
Secondary outcome [28] 0 0
Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status - Clinical benefit: participants with CR, PR, or SD for =>6-month period. FISH testing measures the amount of the HER2 gene in each cell. This gene is responsible for the overproduction of the HER2 protein. FISH-positive: excessive amounts of the gene are present; FISH-negative: normal levels of the gene are present.
Timepoint [28] 0 0
Up to 46 months
Secondary outcome [29] 0 0
Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity - IHC is a commonly used test to assess the amount of the HER2 receptor protein on the surface of the cancer cells. The IHC test results in a score of 0 to 3+, which indicates the amount of HER2 receptor protein on the cells in a sample of breast cancer tissue. Tissue scores of 0 to 1+ indicate HER2 negativity; scores of 2+ and 3+ indicate HER2 positivity. Clinical benefit is defined as participants with CR, PR, or SD for =>6-month period.
Timepoint [29] 0 0
Up to 46 months
Secondary outcome [30] 0 0
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 - The HER2 ECD is a glycoprotein that can be shed from the cell surface into the blood of normal individuals and can be elevated in different pathologic conditions. The serum HER2 ECD level generally reflects the tissue HER2 status. The HER2 ECD is quantified in serum with an enzyme-linked immunosorbent assay (ELISA). Non-Evaluable (NE): any participant who could not be classified as CR, PR, SD, or PD.
Timepoint [30] 0 0
Up to 46 months
Secondary outcome [31] 0 0
Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive - Participants who had a HER2-negative tumor status based on baseline tissue with baseline serum HER2 ECD values =<15 ng/mL but later had at least two consecutive serum HER2 ECD values >15 ng/mL experienced seroconversion.
Timepoint [31] 0 0
Up to 46 months
Secondary outcome [32] 0 0
Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive - Time to seroconversion was defined as the time from the date of randomization until the first instance of serum HER2 (>15 ng/mL) on two consecutive occasions.
Timepoint [32] 0 0
Up to 46 months
Secondary outcome [33] 0 0
Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline - EGFR is a cell surface receptor tyrosine kinase expressed in certain types of tumors. Depending upon the staining intensity, EGFR was graded as follows: 0=absence of membrane staining above background in all tumor cells; EGFR-positive=staining is defined as any IHC staining of tumor cell membranes above background level, whether it is complete or incomplete circumferential staining (1+, 2+, 3+).
Timepoint [33] 0 0
Baseline

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Garran
Recruitment hospital [2] 0 0
Novartis Investigative Site - Douglas
Recruitment hospital [3] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [4] 0 0
Novartis Investigative Site - Redcliffe
Recruitment hospital [5] 0 0
Novartis Investigative Site - Adelaide
Recruitment postcode(s) [1] 0 0
2606 - Garran
Recruitment postcode(s) [2] 0 0
4814 - Douglas
Recruitment postcode(s) [3] 0 0
4029 - Herston
Recruitment postcode(s) [4] 0 0
4020 - Redcliffe
Recruitment postcode(s) [5] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Iowa
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
Nebraska
Country [17] 0 0
United States of America
State/province [17] 0 0
Nevada
Country [18] 0 0
United States of America
State/province [18] 0 0
New Jersey
Country [19] 0 0
United States of America
State/province [19] 0 0
New Mexico
Country [20] 0 0
United States of America
State/province [20] 0 0
New York
Country [21] 0 0
United States of America
State/province [21] 0 0
North Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
North Dakota
Country [23] 0 0
United States of America
State/province [23] 0 0
Ohio
Country [24] 0 0
United States of America
State/province [24] 0 0
Pennsylvania
Country [25] 0 0
United States of America
State/province [25] 0 0
South Carolina
Country [26] 0 0
United States of America
State/province [26] 0 0
Tennessee
Country [27] 0 0
United States of America
State/province [27] 0 0
Texas
Country [28] 0 0
United States of America
State/province [28] 0 0
Utah
Country [29] 0 0
United States of America
State/province [29] 0 0
Vermont
Country [30] 0 0
United States of America
State/province [30] 0 0
Virginia
Country [31] 0 0
United States of America
State/province [31] 0 0
Washington
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/show/NCT00073528
Trial related presentations / publications
Schwartzberg LS, Franco SX, Florance A, O'Rourke L, Maltzman J, Johnston S. Lapatinib plus letrozole as first-line therapy for HER-2+ hormone receptor-positive metastatic breast cancer. Oncologist. 2010;15(2):122-9. doi: 10.1634/theoncologist.2009-0240. Epub 2010 Feb 15. Erratum in: Oncologist. 2010;15(3):327. Schwarzberg, Lee S [corrected to Schwartzberg, Lee S].
Sherrill B, Amonkar MM, Sherif B, Maltzman J, O'Rourke L, Johnston S. Quality of life in hormone receptor-positive HER-2+ metastatic breast cancer patients during treatment with letrozole alone or in combination with lapatinib. Oncologist. 2010;15(9):944-53. doi: 10.1634/theoncologist.2010-0012. Epub 2010 Aug 26.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries