Trial Outcomes & Findings for A Study of Herceptin (Trastuzumab)and Biomarkers in Patients With HER2-Positive Metastatic Breast Cancer (NCT NCT00885755)
NCT ID: NCT00885755
Last Updated: 2018-03-29
Results Overview
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 \<median and ≥median membrane H score, phosphatase and tensin homolog gene (PTEN) \<median and ≥median cytoplasm H score, HER2 \<median and ≥median membrane H score, phosphatidylinositol-3-kinase (PI3K) catalytic subunit wild type (WT) and mutation (M), and FC gamma receptors IIIa homozygous Phenyl alanine (FF), heterozygous Phenyl alanine/Valine (VF) and homozygous Valine (VV), receptor IIa Phenotypes homozygous Histidine (HH), heterozygous Histidine/Arginine (HR) and homozygous Arginine (RR) IIb phenotypes homozygous Isoleucien (II),heterozygous Isoleucine/Threonine (IT) and homozygous Threonine (TT) .
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
33 participants
Primary outcome timeframe
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
Results posted on
2018-03-29
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Part I: Trastuzumab+Taxane
STARTED
|
31
|
1
|
1
|
|
Part I: Trastuzumab+Taxane
COMPLETED
|
13
|
1
|
0
|
|
Part I: Trastuzumab+Taxane
NOT COMPLETED
|
18
|
0
|
1
|
|
Part II: Trastuzumab + Capecitabine.
STARTED
|
13
|
1
|
0
|
|
Part II: Trastuzumab + Capecitabine.
COMPLETED
|
8
|
1
|
0
|
|
Part II: Trastuzumab + Capecitabine.
NOT COMPLETED
|
5
|
0
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
|---|---|---|---|
|
Part I: Trastuzumab+Taxane
Adverse Event
|
1
|
0
|
0
|
|
Part I: Trastuzumab+Taxane
Unknown Reason
|
16
|
0
|
0
|
|
Part I: Trastuzumab+Taxane
Sufficient Response Achieved
|
1
|
0
|
0
|
|
Part I: Trastuzumab+Taxane
Death
|
0
|
0
|
1
|
|
Part II: Trastuzumab + Capecitabine.
Unknown Reason
|
5
|
0
|
0
|
Baseline Characteristics
A Study of Herceptin (Trastuzumab)and Biomarkers in Patients With HER2-Positive Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=31 Participants
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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
No Group
n=1 Participants
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.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 11.73 • n=5 Participants
|
37.0 years
STANDARD_DEVIATION NA • n=7 Participants
|
85.0 years
STANDARD_DEVIATION NA • n=5 Participants
|
55.9 years
STANDARD_DEVIATION 12.91 • n=4 Participants
|
|
Sex: Female, Male
Female
|
31 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: 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 monthsPopulation: 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.
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 \<median and ≥median membrane H score, phosphatase and tensin homolog gene (PTEN) \<median and ≥median cytoplasm H score, HER2 \<median and ≥median membrane H score, phosphatidylinositol-3-kinase (PI3K) catalytic subunit wild type (WT) and mutation (M), and FC gamma receptors IIIa homozygous Phenyl alanine (FF), heterozygous Phenyl alanine/Valine (VF) and homozygous Valine (VV), receptor IIa Phenotypes homozygous Histidine (HH), heterozygous Histidine/Arginine (HR) and homozygous Arginine (RR) IIb phenotypes homozygous Isoleucien (II),heterozygous Isoleucine/Threonine (IT) and homozygous Threonine (TT) .
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=27 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part I: Progression Free Survival (PFS) by Biomarker
p95 HER2 +ve (n=9,0)
|
NA months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
IGF1R <median (n=12,0)
|
12.649 months
Interval 4.698 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
c-MET <median (n=10,1)
|
18.595 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
PI3K Amino Acids M (n=9,0)
|
22.407 months
Interval 4.698 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V FF (n=9,0)
|
10.612 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V VF (n=5,1)
|
11.335 months
Interval 9.528 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V VV (n=4,0)
|
22.407 months
Interval 22.209 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H HR (n=8,1)
|
22.209 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIb I232T IT (n=1,0)
|
NA months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
p95 HER2 -ve (n=15,1)
|
13.963 months
Interval 7.261 to 22.407
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
IGF1R ≥median (n=14,1)
|
22.209 months
Interval 7.261 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
c-MET ≥median (n=15,0)
|
13.733 months
Interval 7.031 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
PTEN <median (n=12,0)
|
22.209 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
PTEN ≥median (n=14,1)
|
13.963 months
Interval 6.374 to 31.179
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
HER2 <median (n=11,1)
|
13.733 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
HER2 ≥median (n=14,0)
|
22.209 months
Interval 7.031 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
PI3K Amino Acids WT (n=17,1)
|
13.848 months
Interval 7.261 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H HH (n=3,0)
|
NA months
Interval 9.528 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H RR (n=8,0)
|
13.963 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIb I232T II (n=12,1)
|
11.335 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIb I232T TT (n=1,0)
|
NA months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
PRIMARY outcome
Timeframe: 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 monthsPopulation: PP population; n = number of participants with biomarker data available for the specified 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 \<median and ≥ median membrane H score, c-MET \<median and ≥median membrane H score, PTEN \<median and ≥median cytoplasm H score, HER2 \<median and ≥median membrane H score, PI3K catalytic subunit WT and M, and FC gamma receptors IIIa, IIa and IIb Phenotypes FF, VF and VV, HH, HR and RR, and II, IT and TT.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=27 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part II: Progression Free Survival (PFS) by Biomarker
p95 +ve (n=2,0)
|
8.148 months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
IGF1R <median (n=4,0)
|
8.115 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
IGF1R ≥median (n=4,1)
|
4.074 months
Interval 1.971 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
c-MET<median (n=3,1)
|
4.698 months
Interval 3.45 to 4.698
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
PTEN <median (n=4,0)
|
4.698 months
Interval 1.971 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
HER2 <median (n=2,1)
|
8.148 months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
PI3K Amino Acids WT (n=10,1)
|
5.651 months
Interval 1.971 to 24.214
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V FF (n=4,0)
|
4.320 months
Interval 0.854 to 8.148
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V VF (n=2,1)
|
13.832 months
Interval 3.45 to 24.214
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIIa F176V VV (n=2,0)
|
NA months
Data are not available since there was no evaluable participant.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H HH (n=1,0)
|
3.450 months
Confidence Interval was not applicable since there was only 1 participant.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
p95 -ve (n=5,1)
|
3.450 months
Interval 0.854 to 8.115
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
c-MET≥median (n=4,0)
|
5.043 months
Interval 0.854 to 8.148
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
PTEN ≥median (n=3,1)
|
3.450 months
Interval 0.854 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
HER2 ≥median (n=5,0)
|
3.450 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
PI3K Amino Acids M (n=2,0)
|
4.485 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H HR (n=5,1)
|
8.115 months
Interval 0.854 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIa R166H RR (n=3,0)
|
5.651 months
Interval 2.99 to 24.214
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: Progression Free Survival (PFS) by Biomarker
FC Gamma Receptor IIb I232T II (n=7,1)
|
5.651 months
Interval 0.854 to 24.214
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
PRIMARY outcome
Timeframe: 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 weeksPopulation: PP population; n = number of participants with biomarker data available for the specified 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 \<median and ≥median, c-MET \<median and ≥median, PTEN \<median and ≥median, HER2 \<median and ≥median, PI3K catalytic subunit WT and M, and FC gamma receptors IIIa, IIa and IIb Phenotypes FF, VF and VV, HH, HR and RR, and II, IT and TT . The correlation between the biomarker variables and TTP were investigated using a univariate Cox regression model and time-to-event methods (Kaplan-Meier).
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=27 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part I: Time to Progression (TTP) by Biomarker
IGF1R <median (n=12,0)
|
11.335 months
Interval 4.698 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
IGF1R ≥median (n=14,1)
|
22.407 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
c-MET ≥median (n=15,0)
|
22.209 months
Interval 6.374 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
HER2 <median (n=11,1)
|
NA months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
PI3K Amino Acids WT (n=17,1)
|
13.963 months
Interval 7.261 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
PI3K Amino Acids M (n=9,00)
|
22.407 months
Interval 4.698 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIa R166H HH (n=3,0)
|
NA months
Interval 9.528 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
p95 +ve (n=9,0)
|
NA months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
p95 -ve (n=15,1)
|
13.963 months
Interval 7.261 to 22.407
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
c-MET <median (n=10,1)
|
31.179 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
PTEN <median (n=12,0)
|
22.209 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
PTEN ≥median (n=14,1)
|
13.963 months
Interval 6.374 to 31.179
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
HER2 ≥median (n=14,0)
|
22.209 months
Interval 7.031 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIIa F176V FF (n=9,0)
|
13.963 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIIa F176V VF (n=5,1)
|
11.335 months
Interval 9.528 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIIa F176V VV (n=4,0)
|
22.407 months
Interval 22.209 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIa R166H HR (n=8,1)
|
22.209 months
Interval 3.384 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIa R166H RR (n=8,0)
|
13.963 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIb I232T II (n=12,1)
|
13.963 months
Interval 5.914 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.216 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIb I232T IT (n=1,0)
|
NA months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part I: Time to Progression (TTP) by Biomarker
FC Gamma Receptor IIb I232T TT (n=1,0)
|
NA months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
PRIMARY outcome
Timeframe: 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 monthsPopulation: PP population; n = number of participants with biomarker data available for the specified 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 \<median and ≥median, c-MET \<median and ≥median, PTEN \<median and ≥median, HER2 \<median and ≥median, PI3K catalytic subunit WT and M, and FC gamma receptors IIIa, IIa and IIb Phenotypes FF, VF and VV, HH, HR and RR, and II, IT and TT .
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=27 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part II: TTP by Biomarker
p95 HER2 -ve (n=5,1)
|
3.450 months
Interval 0.854 to 8.115
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
IGF1R <median (n=4,0)
|
8.115 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
c-MET <median (n=3,1)
|
4.698 months
Interval 3.45 to 4.698
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
c-MET ≥median (n=4,0)
|
5.043 months
Interval 0.854 to 8.148
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
PTEN <median (n=4,0)
|
4.698 months
Interval 1.971 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
PI3K Amino Acids M (n=2,0)
|
4.485 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIIa F176V VF (n=2,1)
|
NA months
Interval 3.45 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIIa F176V VV (n=2,0)
|
NA months
Data are not available since there was no evaluable participant.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIa R166H HH (n=1,0)
|
3.450 months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
p95 HER2 +ve (n=2,0)
|
8.148 months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
IGF1R ≥median (n=4,1)
|
4.074 months
Interval 1.971 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
PTEN ≥median (n=3,1)
|
3.450 months
Interval 0.854 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
HER2 <median (n=2,1)
|
8.148 months
Estimate Not Available due to insufficient follow-up to allow estimation.
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
HER2 ≥median (n=5,0)
|
3.450 months
Interval 0.854 to 8.115
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
PI3K Amino Acids WT (n=10,1)
|
5.651 months
Interval 1.971 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIIa F176V FF (n=4,0)
|
4.320 months
Interval 0.854 to 8.148
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIa R166H HR (n=5,1)
|
8.115 months
Interval 0.854 to 8.148
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIa R166H RR (n=3,0)
|
5.651 months
Interval 2.99 to 5.651
|
NA months
Data are not available since there was no evaluable participant.
|
|
Part II: TTP by Biomarker
FC Gamma Receptor IIb I232T II (n=7,1)
|
5.651 months
Interval 0.854 to 8.115
|
13.832 months
Confidence Interval was not applicable since there was only 1 participant.
|
PRIMARY outcome
Timeframe: 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 weeksPopulation: 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.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=19 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
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
c-MET <median CR (n=6)
|
0.0 percentage of participants
|
—
|
|
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
PTEN ≥median SD (n=12)
|
18.2 percentage of participants
|
—
|
|
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
PTEN ≥median PD (n=12)
|
9.1 percentage of participants
|
—
|
|
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
HER2 ≥median PD (n=10)
|
0.0 percentage of participants
|
—
|
|
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
PI3K Amino Acids WT PR (n=11,0)
|
90.0 percentage of participants
|
—
|
|
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
PI3K Amino Acids WT PD (n=11)
|
10.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V FF SD (n=6)
|
16.7 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HH CR (n=3)
|
33.3 percentage of participants
|
—
|
|
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
p95 HER2 +ve CR (n=5)
|
0.0 percentage of participants
|
—
|
|
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
p95 HER2 +ve PR (n=5)
|
25.0 percentage of participants
|
—
|
|
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
p95 HER2 +ve SD (n=5)
|
50.0 percentage of participants
|
—
|
|
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
p95 HER2 +ve PD (n=5)
|
25.0 percentage of participants
|
—
|
|
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
p95 HER2 -ve CR (n=12)
|
0.0 percentage of participants
|
—
|
|
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
p95 HER2 -ve PR (n=12)
|
91.7 percentage of participants
|
—
|
|
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
p95 HER2 -ve SD (n=12)
|
8.3 percentage of participants
|
—
|
|
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
p95 HER2 -ve PD (n=12)
|
0.0 percentage of participants
|
—
|
|
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
IGF1R < median CR (n=9)
|
0.0 percentage of participants
|
—
|
|
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
IGF1R < median PR (n=9)
|
62.5 percentage of participants
|
—
|
|
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
IGF1R < median SD (n=9)
|
37.5 percentage of participants
|
—
|
|
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
IGF1R < median PD (n=9)
|
0.0 percentage of participants
|
—
|
|
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
IGF1R ≥median CR (n=9)
|
0.0 percentage of participants
|
—
|
|
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
IGF1R ≥median PR (n=9,0)
|
88.9 percentage of participants
|
—
|
|
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
IGF1R ≥median SD (n=9)
|
0.0 percentage of participants
|
—
|
|
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
IGF1R ≥median PD (n=9)
|
11.1 percentage of participants
|
—
|
|
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
c-METt <median PR (n=6)
|
83.3 percentage of participants
|
—
|
|
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
c-MET <median SD (n=6)
|
0.0 percentage of participants
|
—
|
|
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
c-MET <median PD (n=6)
|
16.7 percentage of participants
|
—
|
|
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
c-MET ≥median CR (n=11)
|
0.0 percentage of participants
|
—
|
|
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
c-MET ≥median PR (n=11)
|
70.0 percentage of participants
|
—
|
|
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
c-MET ≥median SD (n=11)
|
30.0 percentage of participants
|
—
|
|
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
c-MET ≥median PD (n=11)
|
0.0 percentage of participants
|
—
|
|
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
PTEN <median CR (n=6)
|
0.0 percentage of participants
|
—
|
|
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
PTEN <median PR (n=6)
|
83.3 percentage of participants
|
—
|
|
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
PTEN <median SD (n=6)
|
16.7 percentage of participants
|
—
|
|
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
PTEN <median PD (n=6)
|
0.0 percentage of participants
|
—
|
|
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
PTEN ≥median CR (n=12)
|
0.0 percentage of participants
|
—
|
|
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
PTEN ≥median PR (n=12)
|
72.7 percentage of participants
|
—
|
|
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
HER2 <median CR (n=8)
|
0.0 percentage of participants
|
—
|
|
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
HER2 <median PR (n=8)
|
75.0 percentage of participants
|
—
|
|
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
HER2 <median SD (n=8)
|
12.5 percentage of participants
|
—
|
|
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
HER2 <median PD (n=8)
|
12.5 percentage of participants
|
—
|
|
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
HER2 ≥median CR (n=10)
|
0.0 percentage of participants
|
—
|
|
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
HER2 ≥median PR (n=10)
|
77.8 percentage of participants
|
—
|
|
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
HER2 ≥median SD (n=10)
|
22.2 percentage of participants
|
—
|
|
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
PI3K Amino Acids WT CR (n=11)
|
0.0 percentage of participants
|
—
|
|
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
PI3K Amino Acids WT SD (n=11)
|
0.0 percentage of participants
|
—
|
|
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
PI3K Amino Acids M CR (n=7)
|
0.0 percentage of participants
|
—
|
|
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
PI3K Amino Acids M PR (n=7,0)
|
57.1 percentage of participants
|
—
|
|
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
PI3K Amino Acids M SD (n=7)
|
42.9 percentage of participants
|
—
|
|
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
PI3K Amino Acids M PD (n=7)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V FF CR (n=6)
|
16.7 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V FF PR (n=6)
|
50.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V FF PD (n=6)
|
16.7 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VF CR (n=4)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VF PR (n=4)
|
66.7 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VF SD (n=4)
|
33.3 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VF PD (n=4)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VV CR (n=2)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VV PR (n=2)
|
100.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VV SD (n=2)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIIa F176V VV PD (n=2)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HH PR (n=3)
|
66.7 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HH SD (n=3)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HH PD (n=3)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HR CR (n=5)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HR PR (n=5)
|
25.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HR SD (n=5)
|
50.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H HR PD (n=5)
|
25.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H RR CR (n=5)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H RR PR (n=5)
|
80.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H SD RR (n=5)
|
20.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIa R166H RR PD (n=5)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T II CR (n=8)
|
12.5 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T II PR (n=8)
|
50.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T II SD (n=8)
|
37.5 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T II PD (n=8)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T IT CR (n=1)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T IT PR (n=1)
|
100.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T IT SD (n=1)
|
0.0 percentage of participants
|
—
|
|
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
FC Gamma Receptor IIb I232T IT PD (n=1)
|
0.0 percentage of participants
|
—
|
PRIMARY outcome
Timeframe: 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 monthsPopulation: 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.
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 (\<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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=19 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R ≥median SD (n=3)
|
66.7 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET <median PD (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET ≥median CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 ≥median PD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V FF CR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VV PD (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HH SD (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H RR PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T II CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T II PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T II SD (n=4)
|
75.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T II PD (n=4)
|
25.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T IT CR (N=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T IT PR (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T IT SD (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T TT CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T TT PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T TT SD (n=4)
|
75.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T TT PD (n=4)
|
25.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 +ve CR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 +ve PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 +ve SD (n=2)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 +ve PD (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 -ve CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 -ve PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 -ve SD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
p95 HER2 -ve PD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R <median CR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R <median PR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R <median SD (n=3)
|
66.7 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R <median PD (n=3)
|
33.3 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R ≥median CR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R ≥median PR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
IGF1R ≥median PD (n=3)
|
33.3 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET <median CR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET <median PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET <median SD (n=2)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET ≥median PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET ≥median SD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
c-MET ≥median PD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN <median CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN <median PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN <median SD (n=4)
|
75.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN <median PD (n=4)
|
25.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN ≥median CR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN ≥median PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN ≥median SD (n=2)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PTEN ≥median PD (n=2)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 <median CR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 <median PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 <median SD (n=2)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 <median PD (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 ≥median CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 ≥median PR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
HER2 ≥median SD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids WT CR (n=7)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids WT PR (n=7)
|
14.3 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids WT SD (n=7)
|
71.4 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids WT PD (n=7)
|
14.3 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids M CR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids M PR (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids M SD (n=2)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
PI3K Amino Acids M PD (n=2)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V FF PR (n=3)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V FF SD (n=3)
|
66.7 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V FF PD (n=3)
|
33.3 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VF CR (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VF PR (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VF SD (n=1)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VF PD (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VV CR (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VV PR (n=1)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIIa F176V VV SD (n=1)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HH CR (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HH PR (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HH PD (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HR CR (n=5)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HR PR (n=4)
|
25.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HR SD (n=4)
|
50.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H HR PD (n=4)
|
25.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H RR CR (n=4)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H RR SD (n=2)
|
100.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIa R166H RR PD (n=2)
|
0.0 percentage of participants
|
—
|
|
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
FC Gamma Receptor IIb I232T IT PD (n=0)
|
NA percentage of participants
Data are not available since there was no evaluable participant.
|
—
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; Participant from Group B and from No group were not included in this analysis.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=31 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part I: TTP in Intent to Treat (ITT) Population
|
22.21 months
Interval 9.53 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.22 months
Confidence Interval was not applicable since there was only 1 participant.
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; Participant from Group B and from No group were not included in this analysis.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=31 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part I: PFS in ITT Population
|
18.60 months
Interval 8.08 to
Estimate Not Available due to insufficient follow-up to allow estimation.
|
1.22 months
Confidence Interval was not applicable since there was only 1 participant.
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; Participant from Group B and from No group were not included in this analysis.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=13 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part II: TTP in Intent to Treat (ITT) Population
|
5.65 months
Interval 2.99 to 8.15
|
13.83 months
Confidence Interval was not applicable since there was only 1 participant.
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; Participant from Group B and from No group were not included in this analysis.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=13 Participants
This group included participants who progressed after at least 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.
|
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks
n=1 Participants
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.
|
|---|---|---|
|
Part II: PFS in ITT Population
|
5.65 months
Interval 2.99 to 24.21
|
13.83 months
Confidence Interval was not applicable since there was only 1 participant.
|
SECONDARY outcome
Timeframe: 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)Population: PP population
Overall survival was calculated in months from the day of screening until death.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=27 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
Overall Survival in Per Protocol Population
|
36.40 months
Interval 6.57 to 40.28
|
—
|
SECONDARY outcome
Timeframe: 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)Population: ITT population
Overall survival was calculated in months from the day of screening until death.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=31 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
Overall Survival in ITT Population
|
NA months
Interval 6.57 to 40.28
Estimate Not Available due to insufficient follow-up to allow estimation.
|
—
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; n = number of participants analyzed for the specified category.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=20 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part I: Responders (n=20)
|
75.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part I: Non-Responders (n=20)
|
20.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part I: Missing (n=20)
|
5.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part II: Responders (n=9)
|
11.1 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part II: Non-Responders (n=9)
|
88.9 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Part II: Missing (n=9)
|
0.0 percentage of participants
|
—
|
SECONDARY outcome
Timeframe: 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 monthsPopulation: ITT population; n = number of participants analyzed for the specified category.
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.
Outcome measures
| Measure |
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)
n=20 Participants
This group included participants who progressed after at least 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.
|
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.
|
|---|---|---|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part I: SD (n=20)
|
15.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part I: PD (n=20)
|
5.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part I: Missing (n=20)
|
5.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part II: CR (n=9)
|
0.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part II: SD (n=9)
|
66.7 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part II: PD (n=9)
|
22.2 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part I: CR (n=20)
|
5.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part I: PR (n=20)
|
70.0 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part II: PR (n=9)
|
11.1 percentage of participants
|
—
|
|
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Part II: Missing (n=9)
|
0.0 percentage of participants
|
—
|
Adverse Events
All Participants
Serious events: 9 serious events
Other events: 33 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
All Participants
n=33 participants at risk
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.
|
|---|---|
|
General disorders
Pyrexia
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Chest pain
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Medical device complication
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Cellulitis
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Sepsis
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Cardiac disorders
Cardiac failure
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Hip fracture
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Reproductive system and breast disorders
Menorrhagia
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Vascular disorders
Thrombosis
|
3.0%
1/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
Other adverse events
| Measure |
All Participants
n=33 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
60.6%
20/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Nausea
|
60.6%
20/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Vomiting
|
39.4%
13/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Constipation
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Dyspepsia
|
36.4%
12/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Stomatitis
|
24.2%
8/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Abdominal Pain
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Abdominal pain upper
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Haemorrhoids
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Dry mouth
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Gastritis
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Gastrointestinal disorders
Toothache
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Fatigue
|
63.6%
21/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Influenza like illness
|
36.4%
12/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Oedema peripheral
|
33.3%
11/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Asthenia
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Mucosal inflammation
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Pain
|
21.2%
7/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Chest pain
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Oedema
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Axillary pain
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Chest discomfort
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Chills
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
General disorders
Pyrexia
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Rash
|
66.7%
22/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
69.7%
23/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Palmer-plantar erythrodysaesthesia syndrome
|
30.3%
10/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
48.5%
16/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Scab
|
21.2%
7/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Erythema
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Skin and subcutaneous tissue disorders
Onycholsis
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Headache
|
45.5%
15/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
48.5%
16/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Dysgeusia
|
30.3%
10/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Neuropathy peripheral
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Dizziness
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Neurotoxicity
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Polyneuropathy
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Cognitive disorder
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Sinus headache
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Neuralgia
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Nervous system disorders
Restless leg syndrome
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
39.4%
13/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
39.4%
13/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Upper respiratory tract infection
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Nasopharyngitis
|
21.2%
7/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Rhinitis
|
21.2%
7/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Urinary tract infection
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Sinusitis
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Nail infection
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Localised infection
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Nail bed infection
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Respiratory tract infection
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Skin infection
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Herpes simplex
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Hordeolum
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Laryngitis
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Oral herpes
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Tooth abscess
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Infections and infestations
Viral infection
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
30.3%
10/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
30.3%
10/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
18.2%
6/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Procedural pain
|
33.3%
11/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Fall
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Seroma
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Radiation skin injury
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Injury, poisoning and procedural complications
Thermal burn
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Conjunctivitis
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Dry eye
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Lacrimation increased
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Ocular surface disease
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Vision blurred
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Eye disorders
Eye pain
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Vascular disorders
Hot flush
|
27.3%
9/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Vascular disorders
Lymphoedema
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Vascular disorders
Thrombosis
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Vascular disorders
Hypertension
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Psychiatric disorders
Insomnia
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Psychiatric disorders
Anxiety
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Metabolism and nutrition disorders
Decreased appetite
|
36.4%
12/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Reproductive system and breast disorders
Breast pain
|
15.2%
5/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Reproductive system and breast disorders
Menstruation irregular
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Reproductive system and breast disorders
Amenorrhoea
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Blood and lymphatic system disorders
Anaemia
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Blood and lymphatic system disorders
Neutropenia
|
12.1%
4/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Immune system disorders
Drug hypersensitivity
|
9.1%
3/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Immune system disorders
Hypersensitivity
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Investigations
Haemoglobin decreased
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Investigations
Ejection fraction decreased
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Investigations
Weight increased
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Cardiac disorders
Palpitations
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
|
Cardiac disorders
Left ventricular dysfunction
|
6.1%
2/33 • From the date of Screening until 4 weeks after the last visit of the participant
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER