Completed

Paclitaxel With / Without GW572016 (Lapatinib) As First Line Therapy For Women With Advanced Or Metastatic Breast Cancer

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What is being tested

Paclitaxel

+ GW572016 (Lapatinib)
Drug
Who is being recruted

Neoplasms, Breast

Over 18 Years

See all eligibility criteria

How is the trial designed

Treatment Study

Placebo-Controlled
Phase 3
Interventional
Study Start: January 2004

See protocol details

Summary

Principal SponsorGlaxoSmithKline
Last updated: May 6, 2015
Sourced from a government-validated database.Claim as a partner
Study start date: January 1, 2004Actual date on which the first participant was enrolled.

The purpose of this study is to determine the efficacy and safety of an oral dual tyrosine kinase inhibitor (GW572016) in combination with paclitaxel compared to paclitaxel alone in first line advanced or metastatic breast cancer.

Official TitleA Randomized, Multicenter, Double-Blind, Placebo-Controlled, 2-Arm, Phase III Study of Oral GW572016 in Combination With Paclitaxel in Subjects Previously Untreated or Advanced or Metastatic Breast Cancer 
Principal SponsorGlaxoSmithKline
Last updated: May 6, 2015
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
580 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a placebo-controlled study, some participants receive the experimental treatment, while others receive an inert substance (placebo) to compare outcomes. This method helps to isolate the effect of the treatment from the psychological effects of receiving any treatment at all.

Other Options
Non-placebo-controlled: No placebo is used. All participants receive the actual treatment or alternative interventions (often the Standard of Care), and comparisons are made between these treatments.

How the interventions assigned to participants is kept confidential
Neither participants nor researchers know who is receiving which treatment. This is the most rigorous way to reduce bias, ensuring that expectations do not influence the results.

Other Ways to Mask Information
Open-label: Everyone knows which treatment is being given.
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
FemaleBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Neoplasms, Breast
Criteria

Inclusion criteria: * Signed Informed Consent * Able to swallow an oral medication * Cardiac ejection fraction within the institutional range of normal as measured by echocardiogram * Adequate kidney and liver function * Adequate bone marrow function * Tumor tissue available for testing * Prior adjuvant or neoadjuvant therapy is permitted with an anthracycline or anthracenedione-containing regimen however, subjects must have had cumulative doses of less than 360 mg/m2 of doxorubicin, 720 mg/m2 of epirubicin, or 72 mg/m2 of mitoxantrone * No Her2/neu overexpression in tumor tissue tested or status unknown if tissue has never been tested Exclusion criteria: * Prior treatment regimens for advanced or metastatic breast cancer. * Pregnant or lactating * Conditions that would effect the absorption of an oral drug * Active infection * Brain metastases * Treatment with EGFR (Endothelial Growth Factor Receptor) inhibitor. * Known hypersensitivity to Taxol or excipients of Taxol * Peripheral neuropathy of Grade 2 or greater is not permitted * Severe Cardiovascular disease or cardiac disease requiring a device. * Serious medical or psychiatric disorder that would interfere with the patient's safety or informed consent.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

50% chance 

of being blinded to the placebo group

Treatment Groups
Group I
Experimental
Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks
Group II
Placebo
Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks and Placebo
Study Objectives
Primary Objectives

Time to progression (TTP) is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The investigator assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors \[RECIST\] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the investigator, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.

Time to progression is defined as the interval between the date of randomization and the earliest date of progression of disease (PD) or death due to breast cancer. The IRC assessed PD based on radiological PD (imaging data) and clinical symptomatic progress (Response Evaluation Criteria in Solid Tumors \[RECIST\] Criteria: target lesion (TL), at least a 20% increase in the sum of largest diameter (LD) of TLs or the appearance of one or more new lesions; non-TL (NTL), the appearance of one or more new lesions and/or unequivocal progression of existing NTLs). TTP was assessed in participants who died due to breast cancer or progressed, as assessed by the independent reviewer, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.
Secondary Objectives

The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The Response Evaluation Criteria in Solid Tumors (RECIST) was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.

The percentage of participants with tumor response is defined as those participants with measurable disease who achieved either a complete response (CR) or partial response (PR). The RECIST criteria was used to evaluate the measurability of tumor lesions, to determine target lesion (TLs) and non-target lesion (NTLs). CR (TLs and NTLs): the disappearance of all TLs and NTLs; PR (for TLs): at least a 30% decrease in the sum of the largest diameter (LD) of TLs, taking as a reference the Baseline sum LD; PR (for NTLs): persistence of one or more lesions.

Percentage of participants. with CB is defined as the percentage of participants with evidence of CR (disappearance of all TLs and NTLs), PR (TLs: a \>=30% decrease in the sum of the LD, taking as a reference the Baseline sum LD; NTLs: persistence of \>=1 lesion), or stable disease (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) for \>=6 months based on RECIST criteria. PD for TL: a \>=20% increase in the sum of the LD of TLs or the appearance of \>=1 new lesion. PD for NTLs: the appearance of \>=1 new lesion and/or unequivocal progression of existing NTLs.

Time to response (TTR) is defined as the time from randomization until the first documented evidence of CR (disappearance of all TLs and NTLs) or PR (for TLs: a \>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; for NTLs: the persistence of \>=1 lesion) (whichever status was recorded first). TTR data are displayed as the number of participants achieving a CR or PR by the indicated week. The investigator evaluated the TTR, and the analysis was based on responses confirmed at a repeat assessment, with the TTR taken as the first time the response was observed.

The investigator evaluated the DOR for the subset of participants who showed a CR (disappearance of all TLs and NTLs) or PR (TLs: a \>=30% decrease in the sum of the LD of TLs, taking as a reference the Baseline sum LD; NTLs: persistence of \>=1 lesion). DOR is defined as the time from the first documented evidence of PR or CR until the first documented sign of PD (TL: a \>=20% increase in the sum of the LD of TLs or the appearance of \>=1 new lesion; NTL: the appearance of \>=1 new lesion and/or unequivocal progression of existing NTLs) or death due to breast cancer, if sooner.

PFS is defined as the interval between the date of randomization and the earliest date of progression disease (PD) or death due to any cause, if sooner. For TLs, progressive disease is defined as at least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. par., participants.

PFS is defined as the interval between the date of randomization and the earliest date of disease progression or death due to any cause, if sooner. Six months PFS is defined as PFS at six months from the time of randomization. Raw data for 6 months PFS are not available; thus, data are presented as the number of participants who progressed or died at or prior to 6 months. For TLs, progressive disease is defined asat least a 20% increase in the sum of the LD of TLs or the appearance of 1 or more new lesions. For NTLs, progressive disease is defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. PFS was assessed in participants who died or progressed, as well as in those who were censored and completed follow-up and those who were censored but are still being followed. For censored participants (those without a documented date of disease progression/death due to breast cancer), the date of the last radiographic assessment was used.

Overall survival is defined as the time from randomization until death due to any cause.

The FACT-B questionnaire was designed to measure multidimensional quality of life (QOL) in participants with breast cancer. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each scored from 0 \[not at all\] to 4 \[very much\] for all subscales); the emotional and social/family well-being (1 question optional) subscale scores range from 0 to 24 (based on 6 questions), and the additional concerns subscale score ranges from 0 to 40, based on 10 questions. The FACT-B Total Score (0 \[better QOL\] to 144 \[worse QOL\]) is the sum of the subscale scores.

The FACT-G questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, social/family, emotional, and functional well-being. The physical, social/family, and functional well-being subscale scores range from 0 to 28, based on responses to 7 questions (each question scored from 0 \[not at all\] to 4 \[very much\]); the emotional well-being subscale score ranges from 0 to 24, based on responses to 6 questions. The FACT-G Total Score (ranging from 0 \[better QOL\] to 108 \[worse QOL\]) is the sum of the subscale scores.

The TOI questionnaire was designed to measure multidimensional QOL in participants with cancer and includes subscales for physical, functional well-being, and additional cancer concerns. The physical and functional well-being subscale scores range from 0 to 28, based on 7 questions (each question scored from 0 \[not at all\] to 4 \[very much\]); the breast cancer unweighted subscale scores range from 0 to 36, based on 9 questions. The total TOI score (ranging from 0 \[better QOL\] to 92 \[worse QOL\]) is the sum of the TOI subscale scores.

The Press Laboratory collected tumor tissues of participants for ErbB2 testing. ErbB2 testing is done to detect breast cancer and predict its likely outcome. All samples were analyzed by the Press Laboratory. Participants were categorized as ErbB2 positive (overexpression of the ErbB2 gene), ErbB2 negative, and assay not done (which included participants with no available samples and those with inconclusive results). ErbB2 status is determined by immunohistochemistry (ICH) assay and fluorescence in situ hybridization (FISH) testing. Negative ErbB2 status is defined as 0 or 1+ by IHC, or as 2+ by IHC and FISH.

The Press Laboratory collected tumor tissues of participants for biomarker testing. All samples were analyzed by the Press Laboratory. The ratio of ErbB2 gene signals to chromosome 17 signals, which indicates the progression of breast cancer, was calculated. Low levels of amplification (few copies) may have a ratio of 2-5, whereas high levels of amplification may have a ratio \>10.

The Press Laboratory tested tumor tissue samples (taken at Screening, prior to randomization to study treatment) to determine intra-tumoral expression levels of ErbB1, ErbB2, and other analytes associated with these pathways by IHC, the process of detecting antigens (e.g., proteins) in cells of a tissue section. The IHC assessment is expressed as: 0, no staining (no cancer cells); 1+, faint staining; 2+, weak to moderate complete staining; 3+, strong complete staining (many cancer cells). A status of "Assay not done" was assigned to participants with no available samples and to those with inconclusive results. If strong staining is observed, breast cancer that has high levels of HER2 expression (overexpression) is indicated. If moderate/weak staining is observed (IHC=2+), breast cancer that has low/moderate expression levels is indicated. When no staining is observed (IHC=0), breast cancer HER2 expression may be below the level of detection of the assay.

The Press Laboratory tested participants who were 2+ (weak to moderate complete staining) or 3+ (strong complete staining) for ErbB2 overexpression by IHC for ErbB2 gene amplification using the FISH assay. The results of the FISH assay can be ErbB2 gene "amplification" (increased number of copies of the ErbB2 gene) or "non-amplification" (not many copies of the ErbB2 gene). A status of "Assay not done" was assigned to those participants with no available samples and to those with inconclusive results (e.g., due to hybridization or staining problems).

The Quest Laboratory collected blood samples for quantitative determination of serum ErbB1. The results of serum monitoring were used to compare tumor response rates following randomized therapy.

The Quest Laboratory collected blood samples for quantitative determination of serum ErbB2. The results of serum monitoring were used to compare tumor response rates following randomized therapy.

The severity of adverse events was graded per the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3. Grades 1 through 5 have unique clinical descriptions of severity for each AE based on the following general guideline: Grade 1, Mild AE; Grade 2, Moderate AE; Grade 3, Severe AE; Grade 4, Life-threatening or disabling AE; Grade 5, death related to AE.

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 177 locations
Suspended
GSK Investigational SiteTucson, United StatesSee the location
Suspended
GSK Investigational SiteHot Springs, United States
Suspended
GSK Investigational SiteJonesboro, United States
Suspended
GSK Investigational SiteFountain Valley, United States
Completed177 Study Centers