A Phase 3 interventional study of Paclitaxel and GW572016 (Lapatinib) in Neoplasms, Breast, sponsored by GlaxoSmithKline. Completed at 177 sites in 25 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-05-06.
Sponsored by GlaxoSmithKline · Phase 3, Interventional, and Treatment
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.
12,544 studies on the registry are indexed under Breast Neoplasms; 2,892 are open to participants now.
This study's enrollment of 580 is above the median of 72 across 9,303 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.
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Exclusion criteria:
Lapatinib 1500 mg, once daily and Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks
Drug: Paclitaxel · Drug: GW572016 (Lapatinib)
Paclitaxel 175 mg/m Intravenously over 3 hours ever 3 weeks and Placebo
Drug: Paclitaxel
Active Comparator
Oral GW572016 Lapatinib
Also known as: Paclitaxel
Time to Progression as Evaluated by the Investigator
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 frame: Randomization until the date of disease progression or death (average of 26 weeks)
Time to Progression as Evaluated by the Independent Review Committee (IRC)
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.
Time frame: Randomization until the date of disease progression or death (average of 26 weeks)
Number of Participants With Tumor Response as Evaluated by the Investigator
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.
Time frame: Randomization until the date of disease progression or death (average of 26 weeks)
Number of Participants With Tumor Response as Evaluated by the Independent Review Committee
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.
Time frame: Randomization until the date of disease progression or death (average of 26 weeks)
Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator
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 frame: Randomization until the date of disease progression or death (average of 26 weeks)
Number of Participants With a Response of CR or PR by the Indicated Study Week
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.
Time frame: Weeks 6, 12, 18, 24, 30, 36, 42, 48, 54, 60, 66, and 72
Duration of Response (DOR)
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.
Time frame: From the time of the first documented complete or partial response until the first documented evidence of progression or death (average of 26 weeks)
Progression-Free Survival (PFS)
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.
Time frame: Randomization until the date of disease progression or death (average of 26 weeks)
Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS)
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.
Time frame: Randomization until the date of disease progression or death (average of 26 weeks)
Overall Survival
Overall survival is defined as the time from randomization until death due to any cause.
Time frame: Randomization until the date of death due to any cause (average of 24 months)
Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire Scores
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.
Time frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Questionnaire 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.
Time frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
Change From Baseline in Trial Outcome Index (TOI) Questionnaire 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.
Time frame: Baseline (Day 1); Weeks 9, 21, 33, and 45; Withdrawal
Number of Participants With the Indicated ErbB2 Status at Baseline
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.
Time frame: Baseline
ErbB2 Ratio
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.
Time frame: Baseline
Number of Participants With the Indicated Immunohistochemistry (IHC) Results at Screening
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.
Time frame: Screening (Day -1)
Number of Participants With the Indicated ErbB2 Fluorescence in Situ Hybridization (FISH) Results
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).
Time frame: Baseline
Serum ErbB1 Concentration
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.
Time frame: Screening (Day-1) and Withdrawal (up to Study Week 129)
Serum ErbB2 Concentration
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.
Time frame: Screening (Day-1) and Withdrawal (up to Study Week 129)
Number of Participants With the Indicated Adverse Events (AEs) With a Maximum Toxicity Grade of 3 or 4
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.
Time frame: Baseline (Day 1) until 30 days after the last dose of randomized therapy (average of 26 weeks)
| Milestone | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Started | 291 | 288 |
| Missing | 26 | 13 |
| Completed | 5 | 4 |
| Not completed | 286 | 284 |
| Withdrew: Withdrawal by subject | 28 | 21 |
| Withdrew: Lost to follow-up | 25 | 28 |
| Withdrew: Protocol violation | 0 | 2 |
| Withdrew: Death | 198 | 215 |
| Withdrew: Other/unknown | 9 | 5 |
| Withdrew: Missing | 26 | 13 |
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.
| weeks | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Time to Progression as Evaluated by the Investigator | 29.0 (13.9 to 46.9) | 22.9 (12.0 to 38.3) |
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.
| weeks | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Time to Progression as Evaluated by the Independent Review Committee (IRC) | 33.7 (18.7 to 69.1) | 26.1 (12.9 to 57.1) |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| CR | 14 | 6 |
| PR | 88 | 67 |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| CR | 1 | 1 |
| PR | 77 | 53 |
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.
| Percentage of participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Percentage of Participants With Clinical Benefit (CB) as Assessed by the Investigator | 40.5 | 31.9 |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Week 6 | 3 | 0 |
| Week 12 | 83 | 55 |
| Week 18 | 86 | 57 |
| Week 24 | 98 | 69 |
| Week 30 | 98 | 69 |
| Week 36 | 101 | 71 |
| Week 42 | 102 | 72 |
| Week 48 | 102 | 72 |
| Week 54 | 102 | 72 |
| Week 60 | 102 | 72 |
| Week 66 | 102 | 72 |
| Week 72 | 102 | 73 |
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.
| weeks | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Duration of Response (DOR) | 28.3 (22.3 to 50.0) | 27.1 (18.1 to 46.3) |
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.
| weeks | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Progression-Free Survival (PFS) | 25.1 (21.9 to 32.1) | 22.6 (21.0 to 25.4) |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Number of Participants Who Progressed or Died at or Prior to 6 Months, as a Measure of Six Months Progression-free Survival (PFS) | 133 | 153 |
Overall survival is defined as the time from randomization until death due to any cause.
| months | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Overall Survival | 23.82 (19.88 to 26.18) | 20.17 (17.84 to 23.92) |
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.
| Scores on a scale | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Week 9, n=208, 230 | -1.1 ± 16.09 | -2.3 ± 16.27 |
| Week 21, n=126, 125 | 1.0 ± 16.63 | -1.3 ± 17.13 |
| Week 33, n=72, 64 | 1.4 ± 17.39 | -2.0 ± 12.75 |
| Week 45, n=35, 38 | 2.3 ± 22.05 | -1.4 ± 10.79 |
| Withdrawal, n=190, 212 | -5.0 ± 19.53 | -8.4 ± 17.99 |
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.
| Scores on a scale | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Week 9, n=213, 232 | -0.7 ± 13.35 | -1.3 ± 13.26 |
| Week 21, n=127, 125 | 0.4 ± 13.97 | -0.2 ± 14.38 |
| Week 33, n=71, 65 | 1.1 ± 14.80 | -1.7 ± 10.81 |
| Week 45, n=34, 39 | 0.9 ± 17.68 | -1.6 ± 10.41 |
| Withdrawal, n=193, 214 | -4.4 ± 16.11 | -7.5 ± 15.02 |
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.
| Scores on a scale | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Week 9, n=208, 232 | -2.3 ± 12.32 | -2.6 ± 11.88 |
| Week 21, n=126, 125 | -0.5 ± 11.99 | -2.7 ± 12.42 |
| Week 33, n=72, 65 | -0.1 ± 12.83 | -2.9 ± 9.05 |
| Week 45, n=36, 38 | 1.5 ± 15.91 | -2.8 ± 8.98 |
| Withdrawal, n=190, 212 | -4.4 ± 14.30 | -6.1 ± 12.84 |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Positive | 52 | 39 |
| Negative | 199 | 202 |
| Assay not done | 40 | 47 |
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.
| ratio of signals | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| ErbB2 Ratio | 2.23 ± 2.301 | 2.14 ± 2.214 |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| 0 | 139 | 139 |
| 1+ | 50 | 51 |
| 2+ | 15 | 22 |
| 3+ | 40 | 28 |
| Assay not done | 47 | 48 |
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).
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Amplified | 45 | 35 |
| Non-amplified | 175 | 165 |
| Assay not done | 71 | 88 |
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.
| Nanograms per milliliter (ng/mL) | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Screening, n=269, 265 | 58.6 ± 20.30 | 59.5 ± 44.20 |
| Withdrawal, n=145, 157 | 59.0 ± 30.22 | 61.5 ± 16.74 |
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.
| ng/mL | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Screening, n=270, 265 | 37.67 ± 95.883 | 36.19 ± 87.629 |
| Withdrawal, n=145, 158 | 37.31 ± 98.257 | 39.95 ± 96.327 |
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.
| participants | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| Diarrhea; Grade 3 | 43 | 4 |
| Diarrhea; Grade 4 | 1 | 0 |
| Alopecia; Grade 3 | 10 | 15 |
| Alopecia; Grade 4 | 0 | 0 |
| Rash; Grade 3 | 15 | 1 |
| Rash; Grade 4 | 0 | 0 |
| Nausea; Grade 3 | 7 | 2 |
| Nausea; Grade 4 | 0 | 0 |
| Myalgia; Grade 3 | 6 | 2 |
| Myalgia; Grade 4 | 0 | 0 |
| Neutropenia; Grade 3 | 30 | 20 |
| Neutropenia; Grade 4 | 23 | 14 |
| Vomiting; Grade 3 | 5 | 4 |
| Vomiting; Grade 4 | 0 | 0 |
| Arthralgia; Grade 3 | 7 | 4 |
| Arthralgia; Grade 4 | 0 | 0 |
| Fatigue; Grade 3 | 5 | 5 |
| Fatigue; Grade 4 | 0 | 0 |
| Asthenia; Grade 3 | 1 | 4 |
| Asthenia; Grade 4 | 1 | 0 |
| Neuropathy; Grade 3 | 7 | 3 |
| Neuropathy; Grade 4 | 0 | 0 |
| Decreased appetite; Grade 3 | 1 | 0 |
| Decreased appetite; Grade 4 | 0 | 0 |
| Pain in extremity; Grade 3 | 2 | 3 |
| Pain in extremity; Grade 4 | 2 | 0 |
| Peripheral sensory neuropathy; Grade 3 | 6 | 4 |
| Peripheral sensory neuropathy; Grade 4 | 0 | 0 |
| Pruritis; Grade 3 | 2 | 0 |
| Pruritis; Grade 4 | 0 | 0 |
| Paraesthesia; Grade 3 | 2 | 1 |
| Paraesthesia; Grade 4 | 0 | 0 |
| Constipation; Grade 3 | 0 | 0 |
| Constipation; Grade 4 | 0 | 0 |
| Cough; Grade 3 | 1 | 1 |
| Cough; Grade 4 | 0 | 0 |
Collected over Serious adverse events (SAEs) and adverse events were collected from the first dose of randomized therapy until 30 days after the last dose of randomized therapy (average of 26 weeks).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Lapatinib With Paclitaxel | — | 103/293 (35.2%) | 287/293 (98%) |
| Placebo With Paclitaxel | — | 63/286 (22%) | 278/286 (97.2%) |
| Event | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| DiarrheaGastrointestinal disorders | 24/293 | 2/286 |
| NeutropeniaBlood and lymphatic system disorders | 22/293 | 14/286 |
| Febrile neutropeniaBlood and lymphatic system disorders | 10/293 | 3/286 |
| PyrexiaGeneral disorders | 7/293 | 2/286 |
| Mucosal inflammationGeneral disorders | 6/293 | 1/286 |
| Ejection fraction decreasedInvestigations | 5/293 | 5/286 |
| VomitingGastrointestinal disorders | 4/293 | 4/286 |
| HypercalcemiaMetabolism and nutrition disorders | 4/293 | 3/286 |
| DehydrationMetabolism and nutrition disorders | 4/293 | 0/286 |
| RashSkin and subcutaneous tissue disorders | 4/293 | 0/286 |
| Event | Lapatinib With Paclitaxel | Placebo With Paclitaxel |
|---|---|---|
| AlopeciaSkin and subcutaneous tissue disorders | 153/293 | 183/286 |
| DiarrheaGastrointestinal disorders | 171/293 | 73/286 |
| RashSkin and subcutaneous tissue disorders | 145/293 | 66/286 |
| NauseaGastrointestinal disorders | 100/293 | 85/286 |
| MyalgiaMusculoskeletal and connective tissue disorders | 94/293 | 74/286 |
| NeutropeniaBlood and lymphatic system disorders | 76/293 | 58/286 |
| VomitingGastrointestinal disorders | 74/293 | 48/286 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 70/293 | 58/286 |
| FatigueGeneral disorders | 65/293 | 61/286 |
| AstheniaGeneral disorders | 62/293 | 36/286 |
| Age, Continuous(Years) | Lapatinib With Paclitaxel | Placebo With Paclitaxel | Total |
|---|---|---|---|
| Mean | 51.3 ± 10.45 | 52.4 ± 10.98 | 51.8 ± 10.72 |
| Sex: Female, Male(Participants) | Lapatinib With Paclitaxel | Placebo With Paclitaxel | Total |
|---|---|---|---|
| Female | 291 | 288 | 579 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(participants) | Lapatinib With Paclitaxel | Placebo With Paclitaxel | Total |
|---|---|---|---|
| White | 190 | 182 | 372 |
| Black | 10 | 10 | 20 |
| Asian | 30 | 35 | 65 |
| American Hispanic | 54 | 53 | 107 |
| Unknown | 7 | 8 | 15 |
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