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| ID | Type | Description | Link |
|---|---|---|---|
| 2008-004013-94 |
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This single arm study will evaluate alterations in molecular marker expression in HER2-positive targeted therapy, and will evaluate the effect of continued treatment with Herceptin and Xeloda beyond progression following initial Herceptin-taxane chemotherapy. Patients who develop progressive disease will receive first-line Herceptin (8mg/kg iv loading dose and 6mg/kg iv every 3 weeks) + taxane therapy. patients who develop progressive disease within 9 weeks of treatment will continue treatment with Herceptin in combination with Xeloda (1000mg/m2 po bid on days 1-14 of each 3-week cycle).Biopsies of tumor tissue will be taken for biomarker and gene profiling evaluation. The anticipated time on study treatment is until disease progression, intolerable side effects or patient choice, and the target sample size is 100 individuals.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Standard taxane therapy | Drug | As prescribed |
| |
| capecitabine [Xeloda] |
| Measure | Description | Time Frame |
|---|---|---|
| Part I: Progression Free Survival (PFS) by Biomarker | Progression was defined as an increase by at least 20 percent (%) from the smallest value in the Sum of Longest Diameter (SLD) of lesions. Biomarkers investigated: p95 human epidermal growth factor receptor 2 (p95HER2) positive (+ve) and negative (-ve) , insulin growth factor-1 receptor (IGF1R) less than (<) median and greater than or equal to (≥) median membrane H score, c-MET \ | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part II: Progression Free Survival (PFS) by Biomarker | PFS was calculated from first study medication in Part II to date of progression or death.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95HER2 +ve and -ve population, IGF1R \ | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part I: Time to Progression (TTP) by Biomarker | Progression was defined as an increase by at least 20% from the smallest value in the SLD of lesions.TTP was determined as the time in months from the date of screening until first progression.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R \ |
| Measure | Description | Time Frame |
|---|---|---|
| Part I: TTP in Intent to Treat (ITT) Population | TTP was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Prince Alfred Hospital; Medical Oncology | Camperdown | New South Wales | 2050 | Australia | ||
| Royal North Shore Hospital; Oncology |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A:Trastuzumab+Taxane /Capecitabine (6 Weeks) | This group included participants who progressed after at least six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 milligrams per square meter (mg/m^2) or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on Body Surface Area (BSA) on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part I: Trastuzumab+Taxane |
|
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| Drug |
1000mg/m2 po bid on days 1-14 of each 3-week cycle (only in patients who have progressed) |
|
| trastuzumab [Herceptin] | Drug | 8mg/kg iv loading dose on day 1 of first 3-week cycle, and 6mg/kg iv on day 1 of each subsequent cycle |
|
| End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks |
| Part II: TTP by Biomarker | TTP was calculated from first study medication in Part II to date of progression. The relationship between TTP and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R \ | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part I: Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progrerssive Disease (PD) by Biomarker | BOR was defined according to the Response Evaluation Criteria In Solid Tumors (RECIST). CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (median/≥median), PI3K catalytic subunit (WT/M), and FC gamma receptors IIIa, IIa and IIb (phenotypes FF, VF, VV, HH, HR, RR and II, IT and TT respectively). The correlation between the biomarker variables and percentage of participants with best response were investigated using a univariate regression analysis. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks |
| Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm.PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (\ | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part I: PFS in ITT Population | PFS was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]).. In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part II: TTP in Intent to Treat (ITT) Population | TTP was calculated from first study medication in Part II to date of progression. In participants with measurable disease progression was defined according to RECIST(SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part II: PFS in ITT Population | PFS was calculated from first study medication in Part II to date of progression or death. In participants with measurable disease progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Overall Survival in Per Protocol Population | Overall survival was calculated in months from the day of screening until death. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months) |
| Overall Survival in ITT Population | Overall survival was calculated in months from the day of screening until death. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months) |
| Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| St Leonards |
| New South Wales |
| 2065 |
| Australia |
| Eastern Health Breast Cancer Research | East Ringwood | Victoria | 3135 | Australia |
| Border Medical Oncology; Murray Valley Private Hospital | Wodonga | Victoria | 3690 | Australia |
| Mount Medical Center | Perth | Western Australia | 6000 | Australia |
| Royal Perth Hospital; Department of Medical Oncology | Perth | Western Australia | 6000 | Australia |
| Hospital Universitario Marques de Valdecilla; Servicio de Oncologia | Santander | Cantabria | 39008 | Spain |
| Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia | Valencia | 46010 | Spain |
| Karolinska Hospital; Oncology - Radiumhemmet | Stockholm | 17176 | Sweden |
| Akademiska sjukhuset, Onkologkliniken | Uppsala | 75185 | Sweden |
| Hull Royal Infirmary | Hull | HU3 2JZ | United Kingdom |
| Christie Hospital; Breast Cancer Research Office | Manchester | M20 4QL | United Kingdom |
| Nottingham City Hospital; Oncology | Nottingham | NG5 1PB | United Kingdom |
| FG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part 1 of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
| FG002 | No Group | This group included participants who died before any study disease assessments or post-baseline biopsies. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Part II: Trastuzumab + Capecitabine. |
|
|
Intent-to-treat (ITT) population: All registered participants were included in the ITT population.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) | This group included participants who progressed after at least six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
| BG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
| BG002 | No Group | This group included participants who died before any on study disease assessments or post-baseline biopsies. In Part 1 of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| 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 | Part I: Progression Free Survival (PFS) by Biomarker | Progression was defined as an increase by at least 20 percent (%) from the smallest value in the Sum of Longest Diameter (SLD) of lesions. Biomarkers investigated: p95 human epidermal growth factor receptor 2 (p95HER2) positive (+ve) and negative (-ve) , insulin growth factor-1 receptor (IGF1R) less than (<) median and greater than or equal to (≥) median membrane H score, c-MET \ | Per Protocol (PP) population included all participants who had received a complete first dose of study medication and had baseline and at least one on-treatment biomarker assessment. Number (n) equals (=) number of participants with biomarker data available for the specified biomarker. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Part I: TTP in Intent to Treat (ITT) Population | TTP was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | ITT population; Participant from Group B and from No group were not included in this analysis. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
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| Primary | Part II: Progression Free Survival (PFS) by Biomarker | PFS was calculated from first study medication in Part II to date of progression or death.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95HER2 +ve and -ve population, IGF1R \ | PP population; n = number of participants with biomarker data available for the specified biomarker. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
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| Primary | Part I: Time to Progression (TTP) by Biomarker | Progression was defined as an increase by at least 20% from the smallest value in the SLD of lesions.TTP was determined as the time in months from the date of screening until first progression.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R \ | PP population; n = number of participants with biomarker data available for the specified biomarker. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks |
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| Secondary | Part I: PFS in ITT Population | PFS was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]).. In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | ITT population; Participant from Group B and from No group were not included in this analysis. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
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| Secondary | Part II: TTP in Intent to Treat (ITT) Population | TTP was calculated from first study medication in Part II to date of progression. In participants with measurable disease progression was defined according to RECIST(SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | ITT population; Participant from Group B and from No group were not included in this analysis. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Part II: PFS in ITT Population | PFS was calculated from first study medication in Part II to date of progression or death. In participants with measurable disease progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment. | ITT population; Participant from Group B and from No group were not included in this analysis. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
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| Secondary | Overall Survival in Per Protocol Population | Overall survival was calculated in months from the day of screening until death. | PP population | Posted | Median | Full Range | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months) |
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| Secondary | Overall Survival in ITT Population | Overall survival was calculated in months from the day of screening until death. | ITT population | Posted | Median | Full Range | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months) |
|
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| Secondary | Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. | ITT population; n = number of participants analyzed for the specified category. | Posted | Number | percentage of participants | End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Part II: TTP by Biomarker | TTP was calculated from first study medication in Part II to date of progression. The relationship between TTP and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R \ | PP population; n = number of participants with biomarker data available for the specified biomarker. | Posted | Median | 95% Confidence Interval | months | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Part I: Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progrerssive Disease (PD) by Biomarker | BOR was defined according to the Response Evaluation Criteria In Solid Tumors (RECIST). CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (median/≥median), PI3K catalytic subunit (WT/M), and FC gamma receptors IIIa, IIa and IIb (phenotypes FF, VF, VV, HH, HR, RR and II, IT and TT respectively). The correlation between the biomarker variables and percentage of participants with best response were investigated using a univariate regression analysis. | PP population; n = number of participants with biomarker data available for the specified biomarker. Data are reported for Group A only as there were no evaluable participants in Group B. | Posted | Number | percentage of participants | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm.PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (\ | PP population; n = number of participants with biomarker data available for the specified biomarker. Data are reported for Group A only as there were no evaluable participants in Group B. | Posted | Number | percentage of participants | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population | Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. | ITT population; n = number of participants analyzed for the specified category. | Posted | Number | percentage of participants | End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months |
|
From the date of Screening until 4 weeks after the last visit of the participant
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | All Participants | In Part 1 of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Trastuzumab was administered according to SMPC. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. in Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. | 9 | 33 | 33 | 33 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Medical device complication | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Oedema | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Palmer-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Scab | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Onycholsis | Skin and subcutaneous tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Neurotoxicity | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Polyneuropathy | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Sinus headache | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Restless leg syndrome | Nervous system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nail infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nail bed infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Herpes simplex | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Hordeolum | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Seroma | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Radiation skin injury | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Thermal burn | Injury, poisoning and procedural complications | MedDRA (15.1) | Non-systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Ocular surface disease | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Lymphoedema | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Menstruation irregular | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Amenorrhoea | Reproductive system and breast disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (15.1) | Non-systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA (15.1) | Non-systematic Assessment |
|
The study was prematurely terminated on December 31, 2012. The end of study follow-up was February 18, 2013.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069287 | Capecitabine |
| D000068878 | Trastuzumab |
| ID | Term |
|---|---|
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D005472 | Fluorouracil |
| D014498 | Uracil |
| D011744 | Pyrimidinones |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| IGF1R <median (n=12,0) |
|
| IGF1R ≥median (n=14,1) |
|
| c-MET <median (n=10,1) |
|
| c-MET ≥median (n=15,0) |
|
| PTEN <median (n=12,0) |
|
| PTEN ≥median (n=14,1) |
|
| HER2 <median (n=11,1) |
|
| HER2 ≥median (n=14,0) |
|
| PI3K Amino Acids WT (n=17,1) |
|
| PI3K Amino Acids M (n=9,0) |
|
| FC Gamma Receptor IIIa F176V FF (n=9,0) |
|
| FC Gamma Receptor IIIa F176V VF (n=5,1) |
|
| FC Gamma Receptor IIIa F176V VV (n=4,0) |
|
| FC Gamma Receptor IIa R166H HH (n=3,0) |
|
| FC Gamma Receptor IIa R166H HR (n=8,1) |
|
| FC Gamma Receptor IIa R166H RR (n=8,0) |
|
| FC Gamma Receptor IIb I232T II (n=12,1) |
|
| FC Gamma Receptor IIb I232T IT (n=1,0) |
|
| FC Gamma Receptor IIb I232T TT (n=1,0) |
|
| Hazard Ratio (HR) |
| 1.19 |
| 2-Sided |
| 95 |
| 0.430 |
| 3.282 |
| Superiority or Other |
| Univariate Cox regression Hazard ratio (Membrane H-Score: \ | Hazard Ratio (HR) | 0.86 | 2-Sided | 95 | 0.306 | 2.425 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Cytoplasm H-Score: \ | Hazard Ratio (HR) | 0.49 | 2-Sided | 95 | 0.164 | 1.453 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Membrane H-Score: < median / ≥median) for the biomarker HER2. | Hazard Ratio (HR) | 1.09 | 2-Sided | 95 | 0.377 | 3.160 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Mutation Status: Wild type / Mutation) for the biomarker PI3K amino acids. | Hazard Ratio (HR) | 1.30 | 2-Sided | 95 | 0.409 | 4.132 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: FF / VF) for the biomarker FC Gamma Receptor IIIa F176V. | Hazard Ratio (HR) | 1.183 | 2-Sided | 95 | 0.226 | 6.197 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: FF / VV) for the biomarker FC Gamma Receptor IIIa F176V. | Hazard Ratio (HR) | 1.989 | 2-Sided | 95 | 0.378 | 10.470 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: VF / VV) for the biomarker FC Gamma Receptor IIIa F176V. | Hazard Ratio (HR) | 1.732 | 2-Sided | 95 | 0.235 | 12.783 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: HH / HR) for the biomarker FC Gamma Receptor IIa R166H. | Hazard Ratio (HR) | 0.576 | 2-Sided | 95 | 0.067 | 4.968 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: HH / RR) for the biomarker FC Gamma Receptor IIa R166H. | Hazard Ratio (HR) | 0.743 | 2-Sided | 95 | 0.082 | 6.720 | Superiority or Other |
| Univariate Cox regression Hazard ratio (Phenotype: HR / RR) for the biomarker FC Gamma Receptor IIa R166H. | Hazard Ratio (HR) | 1.073 | 2-Sided | 95 | 0.274 | 4.199 | Superiority or Other |
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
|
|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
|
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|
| OG001 | Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks | This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation. |
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