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This is an open-label, non-randomized, multi-center study of lapatinib plus paclitaxel to evaluate safety, tolerability and efficacy in Japanese patients with ErbB2 over expressing advanced or metastatic breast cancer. Lapatinib 1500mg/day will be administered in combination with paclitaxel 80mg/m2/week. Lapatinib and paclitaxel will be administered until disease progression or withdrawal from the study due to unacceptable toxicity.
The study will proceed in two phases. The first phase (Phase I part) will lead to evaluate safety and tolerability of lapatinib taken together with paclitaxel in the first 6 subjects. Pharmacokinetic profile also will be evaluated as the secondary objects.
Then the study will move to the next treatment phase (Phase II part) to evaluate further safety and clinical activity, if no major safety concerns are raised during Phase I part. The primary objective of the study is to evaluate overall survival (OS), and the secondary objectives are Objective tumour response rate (ORR), Duration of response, Time to response, Clinical benefit and Progression-free survival (PFS) in 12 subjects.
This is an open-label, single-arm, Phase I/II study to evaluate the efficacy, safety and tolerability of weekly paclitaxel and lapatinib in subjects with ErbB2-overexpressing advanced or metastatic breast cancer who have not received prior therapy for metastatic disease. These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given.
This study consists of the Phase I and Phase II parts:
Phase I part
Tolerability and pharmacokinetics in 6 subjects will be evaluated in Phase I part of study and the tolerability criteria are set as follow:
Tolerability criteria in first cycle; Concerning the safety tolerability of this trial, if 1 out of 6 first enrolled subjects meets the tolerability criteria, the study will proceed to phase II part and the regimen will judged as well tolerable. If 2 subjects meet the tolerability criteria, the sponsor will consult the safety review committee. GSK will finally judge based on the consultation regarding the tolerability and the medical significance.
Grade 4 hematologic toxicities. Thrombocytopenia less than or equal to 25,000/mm3 Grade 3 or 4 and clinically significant non-haematologic toxicities. Inability to start cycle 2 within 2 weeks of scheduled dosing due to unresolved toxicity.
For all 6 subjects enrolled, safety profiles occurred in cycle 1 are closely monitored individually. When considering the appropriateness of study continuation, not only the safety profiles noted in cycle 1 of this study, but also the safety profiles reported from pilot part of EGF104578 study and other relevant studies will be referred in order to make medical decisions.
Phase II part After tolerability in 6 subjects enrolled in Phase I part is confirmed, further 6 subjects to be enrolled for Phase II part (i.e. total of 12 subjects). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. All 12 subjects will be followed for survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lap+weekly Pacli | Experimental | These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib. Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lapatinib in combination with weekly paclitaxel | Drug | These subjects will receive weekly paclitaxel (80 mg/m2 IV for 3 weeks in a 4 week cycle) plus lapatinib (1500 mg once daily, starting on the second day of phase I). Subjects will receive a daily dose of lapatinib until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. Study completion is defined as deaths after administering study treatment for more than once. Subjects will be treated with paclitaxel for standard of 6 cycles, and may be continued at the discretion of investigators. If the subject experiences progression, an unacceptable toxicity related to paclitaxel, or termination of lapatinib therapy, paclitaxel therapy must be terminated any time of study period, even before 6 cycles of paclitaxel are given. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Intolerable Toxicities in Phase I of the Study | Investigational treatment was considered tolerable if one or more of the tolerability criteria were met by none or one of the 6 participants in the first cycle of Phase I. If one or more tolerability criteria were met by two or more participants, the issue was referred to the safety committee. Tolerability criteria for toxicities related to investigational treatment included grade 4 neutropenia persisting for 7 or more days, thrombocytopenia with a platelet count of less than or equal to 25,000/millimeter (mm)^3 , clinically significant Grade 3 or 4 non-haematologic toxicities (excluding nausea) and inability to start cycle 2 within 2 weeks of scheduled dosing due to unresolved toxicity. | 28 days |
| Overall Survival | Overall survival is defined as the time from the start of treatment until death due to any cause. For participants who survived, time to death was censored at the time of the last confirmation of survival. | From the start of treatment until death due to any cause or study close, whichever occurred first (assessed up to a maximum of 1290 Days) |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS is defined as the interval between the start of treatment and the earliest date of radiological disease progression or death due to any cause, whichever occurred first. PFS was based on the investigator's assessment. For participants who survived, time to death was censored at the time of the last confirmation of survival. | From the start of treatment until the earliest date of radiological disease progression or death due to any cause, whichever occured first (up to 1009 Days). |
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Inclusion Criteria:
Prior written consent in participating in the study by the subject or his/her private attorney.
Japanese female >=18 years of age.
Invasive breast cancer with stage IV disease.
Documentation by local laboratory of ErbB2 status by immunohistochemistry (IHC) or amplification by fluorescence in situ hybridization (FISH).
If a taxane had been administered in the neoadjuvant or adjuvant setting, progression must have occurred >12 months after completion of this treatment and the patients recovered from all associated toxicities.
Measurable lesion(s) according to RECIST criteria.
Radiotherapy as palliative treatment for painful metastatic disease is permitted but must have been stopped within 2 weeks prior to initiation of any investigational treatment.
For those patients whose disease is ER+ and/or PR+ one of the following criteria should be met:
Eastern cooperative oncology group (ECOG) Performance status (PS) of 0 or 1.
Able to swallow and retain oral medication.
Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. MUGA scan is accepted in cases where an echocardiogram cannot be performed or is inconclusive.
Adequate organ function.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Aichi | 464-8681 | Japan | |||
| GSK Investigational Site |
Six participants who met the eligibility criteria were enrolled into Phase I of the study. These 6 participants continued treatment into Phase II of the study, into which an additional 6 participants were enrolled. A total of 12 participants were followed until death or withdrawal from the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Lapatinib 1500 mg + Paclitaxel 80 mg/m^2 | Participants received lapatinib 1500 milligrams (mg) once daily (QD) in combination with intravenous (IV) paclitaxel (80 milligrams per meters squared [mg/m^2]) weekly on Day 1, Day 8, and Day 15 of a 4-week cycle until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Lapatinib 1500mg + Paclitaxel 80mg/m^2 | Participants received lapatinib 1500 mg QD in combination with IV paclitaxel 80 mg/m^2 weekly on Day 1, Day 8, and Day 15 of a 4-week cycle until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Intolerable Toxicities in Phase I of the Study | Investigational treatment was considered tolerable if one or more of the tolerability criteria were met by none or one of the 6 participants in the first cycle of Phase I. If one or more tolerability criteria were met by two or more participants, the issue was referred to the safety committee. Tolerability criteria for toxicities related to investigational treatment included grade 4 neutropenia persisting for 7 or more days, thrombocytopenia with a platelet count of less than or equal to 25,000/millimeter (mm)^3 , clinically significant Grade 3 or 4 non-haematologic toxicities (excluding nausea) and inability to start cycle 2 within 2 weeks of scheduled dosing due to unresolved toxicity. | All Subjects Population: all participants who received at least one dose of study medication and participated in Phase I of the study. | Number | Participants | 28 days |
|
Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until 30 days after the last dose (up to 1045 Days).
SAEs and non-serious AEs are reported for members of the All Subjects Population, comprised of all participants who had received at least one dose of the study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lapatinib 1500 mg + Paclitaxel 80 mg/m^2 | Participants received lapatinib 1500 mg QD in combination with IV paclitaxel 80 mg/m^2 weekly on Day 1, Day 8, and Day 15 of a 4-week cycle until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrophil count decreased | Investigations | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000077341 | Lapatinib |
| ID | Term |
|---|---|
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Time to Response | Time to response is defined as the time from the start of treatment until first documented evidence of partial response (PR) or a complete response (CR) (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. | From the start of treatment until the first documented evidence of a PR or CR, whichever status is recorded first (up to 66 Days). |
| Duration of Response | Duration of response is defined as the time from the first documented evidence of a CR or a PR until the first documented sign of disease progression or death due to any cause (whichever occured earlier). The analysis was based on responses as evaluated by the investigator and was confirmed at a repeat assessment, with the duration of response taken from the first time the response was observed. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. | From the first documented evidence of a CR or a PR until the first documented sign of disease progression or death, whichever occurred earlier (up to 953 Days). |
| Number of Partcipants With a Best Overall Response (OR) as Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) | Best OR was defined as the best response recorded from the start of treatment until progressive disease (PD)/death as assessed by the investigator. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. PD is defined as at least a 20% increase in the sum of the LD of target lesions or the appearance of 1 or more new lesions compared to the smallest sum LD recorded since the treatment started. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD compared to the smallest sum LD since the treatment started. Any participant who could not be classified by the four preceding definitions was considered Not evaluable. | From the start of treatment until progressive disease/death (up to 1009 Days). |
| Number of Participants With Clinical Benefit Response (CBR) | CBR is defined using RECIST as the number of participants who received at least one dose of study medication and achieved a best OR classified as CR, PR or SD for at least 6 months (24 weeks), i.e., CR + PR + SD for >=24 weeks. CBR was based on confirmed responses by the investigator. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. PD 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 compared to the smallest sum LD recorded since the treatment started. SD is defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD compared to the smallest sum LD since the treatment started. Any participant who could not be classified by the the four preceding definitions was considered Not evaluable | From the start of treatment until progressive disease/death (up to 1009 Days). |
| Maximum Plasma Concentration (Cmax) of Lapatinib and Paclitaxel | Cmax is defined as the maximum concentration of lapatinib and paclitaxel. Cmax was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
| Area Under the Concentration-time Curve (AUC) (0-24) of Lapatinib and Paclitaxel | AUC is defined as the area under the lapatinib or paclitaxel concentration-time curve from time 0 to 24 hours (hrs). AUC (0-24) was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
| AUC From Time Zero to Infinity (0-INF) of Paclitaxel | AUC(0-INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC (0-INF) was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
| Time to the Maximum Drug Concentration (Tmax) of Lapatinib and Paclitaxel | Tmax is defined as the time to peak concentration from initiation of lapatinib and paclitaxel dosing. Tmax was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
| Distribution Volume at Steady State (Vss) of Paclitaxel | Vss is the volume of distribution at steady state of paclitaxel. Vss was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
| Half-life (t1/2) of Paclitaxel | Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half. T1/2 was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
| Drug Clearance (CL) of Paclitaxel | CL is defined as the volume of plasma in the vascular compartment cleared of drug per unit time by the processes of metabolism and excretion. CL was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
| Ehime |
| 791-0280 |
| Japan |
| GSK Investigational Site | Hyōgo | 673-8558 | Japan |
| GSK Investigational Site | Kagoshima | 892-0833 | Japan |
| GSK Investigational Site | Kanagawa | 241-8515 | Japan |
| GSK Investigational Site | Osaka | 540-0006 | Japan |
| GSK Investigational Site | Osaka | 565-0871 | Japan |
| GSK Investigational Site | Saitama | 350-1298 | Japan |
| GSK Investigational Site | Saitama | 362-0806 | Japan |
| GSK Investigational Site | Tokyo | 113-8677 | Japan |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
Participants received lapatinib 1500 mg QD in combination with IV paclitaxel 80 mg/m^2 weekly on Day 1, Day 8, and Day 15 of a 4-week cycle until disease progression or withdrawal from study treatment due to unacceptable toxicity or withdrawal of consent. |
|
|
| Primary | Overall Survival | Overall survival is defined as the time from the start of treatment until death due to any cause. For participants who survived, time to death was censored at the time of the last confirmation of survival. | All Subjects Population: all participants who received at least one dose of study medication | Median | 95% Confidence Interval | Months | From the start of treatment until death due to any cause or study close, whichever occurred first (assessed up to a maximum of 1290 Days) |
|
|
|
| Secondary | Progression-free Survival (PFS) | PFS is defined as the interval between the start of treatment and the earliest date of radiological disease progression or death due to any cause, whichever occurred first. PFS was based on the investigator's assessment. For participants who survived, time to death was censored at the time of the last confirmation of survival. | All Subjects Population. Participants who met the following criteria were censored: no Baseline assessment, no progression, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment started, and death or progression after more than one missed visit. | Median | 95% Confidence Interval | Months | From the start of treatment until the earliest date of radiological disease progression or death due to any cause, whichever occured first (up to 1009 Days). |
|
|
|
| Secondary | Time to Response | Time to response is defined as the time from the start of treatment until first documented evidence of partial response (PR) or a complete response (CR) (whichever status is recorded first). Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the time to response taken as the first time the response was observed. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. | All Subjects Population. Only those participants with a CR or a PR were assessed. | Median | 95% Confidence Interval | Months | From the start of treatment until the first documented evidence of a PR or CR, whichever status is recorded first (up to 66 Days). |
|
|
|
| Secondary | Duration of Response | Duration of response is defined as the time from the first documented evidence of a CR or a PR until the first documented sign of disease progression or death due to any cause (whichever occured earlier). The analysis was based on responses as evaluated by the investigator and was confirmed at a repeat assessment, with the duration of response taken from the first time the response was observed. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. | All Subjects Population. Only those participants with a CR or a PR were assessed. For participants who did not progress or die, duration of response was censored on the date of the last assessment. | Median | 95% Confidence Interval | Months | From the first documented evidence of a CR or a PR until the first documented sign of disease progression or death, whichever occurred earlier (up to 953 Days). |
|
|
|
| Secondary | Number of Partcipants With a Best Overall Response (OR) as Determined by the Response Evaluation Criteria in Solid Tumors (RECIST) | Best OR was defined as the best response recorded from the start of treatment until progressive disease (PD)/death as assessed by the investigator. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. PD is defined as at least a 20% increase in the sum of the LD of target lesions or the appearance of 1 or more new lesions compared to the smallest sum LD recorded since the treatment started. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD compared to the smallest sum LD since the treatment started. Any participant who could not be classified by the four preceding definitions was considered Not evaluable. | All Subjects Population. All participants who received at least one dose of study medication. | Number | Participants | From the start of treatment until progressive disease/death (up to 1009 Days). |
|
|
|
| Secondary | Number of Participants With Clinical Benefit Response (CBR) | CBR is defined using RECIST as the number of participants who received at least one dose of study medication and achieved a best OR classified as CR, PR or SD for at least 6 months (24 weeks), i.e., CR + PR + SD for >=24 weeks. CBR was based on confirmed responses by the investigator. CR is defined as the disappearance of all TLs and non-TLs. PR is defined as at least a 30% decrease in the sum of the LD of the target lesions, taking as a reference, the Baseline sum LD. Baseline measurements were obtained at the Screening Visit. PD 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 compared to the smallest sum LD recorded since the treatment started. SD is defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD compared to the smallest sum LD since the treatment started. Any participant who could not be classified by the the four preceding definitions was considered Not evaluable | All Subjects Population. All participants who received at least one dose of study medication. | Number | Participants | From the start of treatment until progressive disease/death (up to 1009 Days). |
|
|
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| Secondary | Maximum Plasma Concentration (Cmax) of Lapatinib and Paclitaxel | Cmax is defined as the maximum concentration of lapatinib and paclitaxel. Cmax was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | Pharmacokinetic (PK) Population: all participants who provided blood samples for PK evaluation | Geometric Mean | 95% Confidence Interval | Nanogram per milliliter ng/mL | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
|
|
|
| Secondary | Area Under the Concentration-time Curve (AUC) (0-24) of Lapatinib and Paclitaxel | AUC is defined as the area under the lapatinib or paclitaxel concentration-time curve from time 0 to 24 hours (hrs). AUC (0-24) was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation | Geometric Mean | 95% Confidence Interval | hours * nanograms/milliliter (hr*ng/mL) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
|
|
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| Secondary | AUC From Time Zero to Infinity (0-INF) of Paclitaxel | AUC(0-INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. AUC (0-INF) was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation | Geometric Mean | 95% Confidence Interval | hr*ng/mL | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
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| Secondary | Time to the Maximum Drug Concentration (Tmax) of Lapatinib and Paclitaxel | Tmax is defined as the time to peak concentration from initiation of lapatinib and paclitaxel dosing. Tmax was calculated from lapatinib plasma concentration-time data on Day 8 and Day 14 and paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation | Median | Full Range | Hr | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 8 and Day 14 for lapatininb; Day 1 and Day 8 for paclitaxel |
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| Secondary | Distribution Volume at Steady State (Vss) of Paclitaxel | Vss is the volume of distribution at steady state of paclitaxel. Vss was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation | Geometric Mean | 95% Confidence Interval | milliliter per meters squared (mL/m^2) | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
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| Secondary | Half-life (t1/2) of Paclitaxel | Half-life is defined as the time required for the amount of the drug in the plasma to decrease by half. T1/2 was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation | Geometric Mean | 95% Confidence Interval | Hr | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
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| Secondary | Drug Clearance (CL) of Paclitaxel | CL is defined as the volume of plasma in the vascular compartment cleared of drug per unit time by the processes of metabolism and excretion. CL was calculated from paclitaxel plasma concentration-time data on Day 1 and Day 8 with model-independent analyses | PK Population: all participants who provided blood samples for PK evaluation. | Geometric Mean | 95% Confidence Interval | mL/hour/m^2 | Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 1 and Day 8 for paclitaxel |
|
|
|
| 3 |
| 12 |
| 12 |
| 12 |
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Cheilitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Haemorrhoids | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Glossitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Periproctitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Proctalgia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA | Systematic Assessment |
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| Haematocrit decreased | Investigations | MedDRA | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA | Systematic Assessment |
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| Blood albumin decreased | Investigations | MedDRA | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA | Systematic Assessment |
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| White blood cell count decreased | Investigations | MedDRA | Systematic Assessment |
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| Basophil count decreased | Investigations | MedDRA | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA | Systematic Assessment |
|
| Monocyte count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA | Systematic Assessment |
|
| Red blood cell count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood potassium decreased | Investigations | MedDRA | Systematic Assessment |
|
| Blood potassium increased | Investigations | MedDRA | Systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA | Systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA | Systematic Assessment |
|
| Eosinophil count decreased | Investigations | MedDRA | Systematic Assessment |
|
| Neutrophil count increased | Investigations | MedDRA | Systematic Assessment |
|
| White blood cell count increased | Investigations | MedDRA | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Keratolysis exfoliativa acquired | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Pigmentation disorder | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Leukopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Erythropenia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Oedema | General disorders | MedDRA | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA | Systematic Assessment |
|
| Feeling drunk | General disorders | MedDRA | Systematic Assessment |
|
| Feeling hot | General disorders | MedDRA | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA | Systematic Assessment |
|
| Malaise | General disorders | MedDRA | Systematic Assessment |
|
| Paronychia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Gingivitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Erysipelas | Infections and infestations | MedDRA | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nail infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Blepharitis | Eye disorders | MedDRA | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA | Systematic Assessment |
|
| Erythema of eyelid | Eye disorders | MedDRA | Systematic Assessment |
|
| Eyelid oedema | Eye disorders | MedDRA | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Fractured coccyx | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Vaginal discharge | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Vaginal inflammation | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Cardiomegaly | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Meniere's disease | Ear and labyrinth disorders | MedDRA | Systematic Assessment |
|
| Skin papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA | Systematic Assessment |
|
| Neurogenic bladder | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D017437 |
| Skin and Connective Tissue Diseases |
| Title | Measurements |
|---|
|
| PD |
|
| Not evaluable |
|
| Unkown |
|
| Title | Measurements |
|---|---|
|
| Stable disease <=24 weeks |
|
| Progressive disease |
|
| Not evaluable |
|
| Unknown |
|
|
| Paclitaxel 80 mg/m2+ Lapatinib 1500 mg, Day 8 |
|
|
| Paclitaxel 80mg/m^2 + Lapatinib 1500 mg, Day 8 |
|
|
| Paclitaxel 80mg/m^2 + Lapatinib 1500 mg, Day 8 |
|