Breast CancerPhase 2NCT00885755

A Study of Herceptin (Trastuzumab)and Biomarkers in Patients With HER2-Positive Metastatic Breast Cancer

A Phase 2 study testing Standard taxane therapy, capecitabine [Xeloda] and trastuzumab [Herceptin] in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Breast Cancer
What is being tested?: Standard taxane therapy, capecitabine [Xeloda] and trastuzumab [Herceptin]
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 33 participants
Where: 13 sitesin 4 countries
Study dates: 13 Aug 2009to 18 Feb 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
Women only
No healthy volunteers
Adult, Older adult

Who may be able to join

female patients, >=18 years of age;
HER2-positive breast cancer;
al least one metastatic site amenable for core biopsy;
left ventricular ejection fraction >50%.

Who cannot join

prior adjuvant/neoadjuvant Herceptin within past 6 months;
prior adjuvant taxane therapy within past 12 months;
use of chemotherapy, immunotherapy or biological anticancer therapy within past 3 weeks;
known bleeding diatheses.

Trial locations and contacts

13 sites in 4 countries.

Country

City, postcode or hospital

13 sites in 4 countries

Australia6 sites

Royal Prince Alfred Hospital; Medical Oncology
Camperdown, New South Wales, 2050
Eastern Health Breast Cancer Research
East Ringwood, Victoria, 3135
Mount Medical Center
Perth, Western Australia, 6000
Royal Perth Hospital; Department of Medical Oncology
Perth, Western Australia, 6000
Royal North Shore Hospital; Oncology
St Leonards, New South Wales, 2065
Border Medical Oncology; Murray Valley Private Hospital
Wodonga, Victoria, 3690

Other trials in Australia

United Kingdom3 sites

Hull Royal Infirmary
Hull, HU3 2JZ
Christie Hospital; Breast Cancer Research Office
Manchester, M20 4QL
Nottingham City Hospital; Oncology
Nottingham, NG5 1PB

Other trials in United Kingdom

Spain2 sites

Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
Santander, Cantabria, 39008
Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
Valencia, 46010

Other trials in Spain

Sweden2 sites

Karolinska Hospital; Oncology - Radiumhemmet
Stockholm, 17176
Akademiska sjukhuset, Onkologkliniken
Uppsala, 75185

Other trials in Sweden

About this study

Official title: A Prospective Study to Evaluate Alterations in Molecular Biomarkers in HER2 Neu Positive Metastatic Breast Cancer Together With Assessment of Trastuzumab Use Beyond Progression After Initial Response to Trastuzumab-taxane Based Treatment

This single arm study will evaluate alterations in molecular marker expression in HER2-positive targeted therapy, and will evaluate the effect of continued treatment with Herceptin and Xeloda beyond progression following initial Herceptin-taxane chemotherapy. Patients who develop progressive disease will receive first-line Herceptin (8mg/kg iv loading dose and 6mg/kg iv every 3 weeks) + taxane therapy. patients who develop progressive disease within 9 weeks of treatment will continue treatment with Herceptin in combination with Xeloda (1000mg/m2 po bid on days 1-14 of each 3-week cycle).Biopsies of tumor tissue will be taken for biomarker and gene profiling evaluation. The anticipated time on study treatment is until disease progression, intolerable side effects or patient choice, and the target sample size is 100 individuals.

Conditions: Breast Cancer
Being tested: Standard taxane therapy, capecitabine [Xeloda], trastuzumab [Herceptin]
Medical subject headings: Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Standard taxane therapyDrug
As prescribed
capecitabine [Xeloda]Drug
1000mg/m2 po bid on days 1-14 of each 3-week cycle (only in patients who have progressed)
trastuzumab [Herceptin]Drug
8mg/kg iv loading dose on day 1 of first 3-week cycle, and 6mg/kg iv on day 1 of each subsequent cycle

Study groups in NCT00885755
Study group	Role	What they receive
1	Experimental	Not described Receives: Drug: Standard taxane therapy; Drug: capecitabine [Xeloda]; Drug: trastuzumab [Herceptin]

What is being measured

The primary outcome is the main question the study is designed to answer.

Part I: Progression Free Survival (PFS) by Biomarker
Progression was defined as an increase by at least 20 percent (%) from the smallest value in the Sum of Longest Diameter (SLD) of lesions. Biomarkers investigated: p95 human epidermal growth factor receptor 2 (p95HER2) positive (+ve) and negative (-ve) , insulin growth factor-1 receptor (IGF1R) less than (<) median and greater than or equal to (≥) median membrane H score, c-MET <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) .
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part II: Progression Free Survival (PFS) by Biomarker
PFS was calculated from first study medication in Part II to date of progression or death.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95HER2 +ve and -ve population, IGF1R <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.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I: Time to Progression (TTP) by Biomarker
Progression was defined as an increase by at least 20% from the smallest value in the SLD of lesions.TTP was determined as the time in months from the date of screening until first progression.The relationship between PFS and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R <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).
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
Part II: TTP by Biomarker
TTP was calculated from first study medication in Part II to date of progression. The relationship between TTP and the following biomarker variables was investigated in each of study Part 1 and 2: p95 HER2 +ve and -ve population, IGF1R <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 .
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I: Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progrerssive Disease (PD) by Biomarker
BOR was defined according to the Response Evaluation Criteria In Solid Tumors (RECIST). CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (median/≥median), PI3K catalytic subunit (WT/M), and FC gamma receptors IIIa, IIa and IIb (phenotypes FF, VF, VV, HH, HR, RR and II, IT and TT respectively). The correlation between the biomarker variables and percentage of participants with best response were investigated using a univariate regression analysis.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm.PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions. The relationship between best response and the following biomarkers was investigated: p95 HER2 (+ve/-ve), IGF1R, c-MET, PTEN, HER2 (<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.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months

Secondary outcomes (8)

Part I: TTP in Intent to Treat (ITT) Population
TTP was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I: PFS in ITT Population
PFS was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]).. In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part II: TTP in Intent to Treat (ITT) Population
TTP was calculated from first study medication in Part II to date of progression. In participants with measurable disease progression was defined according to RECIST(SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part II: PFS in ITT Population
PFS was calculated from first study medication in Part II to date of progression or death. In participants with measurable disease progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Overall Survival in Per Protocol Population
Overall survival was calculated in months from the day of screening until death.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
Overall Survival in ITT Population
Overall survival was calculated in months from the day of screening until death.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions.
Measured: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Best Overall response was defined according to RECIST. CR: disappearance of all target lesions and all pathological lymph nodes below 10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: At least a 20% increase in the sum of diameters of target lesions, and the sum must also demonstrate an absolute increase of at least 5 mm or persistence of non-target lesions.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Aug 200918 Feb 2013

First posted22 Apr 2009 (estimated)
Study start13 Aug 2009
Primary completion18 Feb 2013
Study completion18 Feb 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Breast CancerStudies of the same condition, open and under way.
More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00885755
Sponsor's protocol ID: MO22004
Other IDs: 2008-004013-94, 2008
Status last verified: Feb 2018
First submitted: 16 Mar 2009
Last updated: 29 Mar 2018
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

All Breast Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Prospective Study to Evaluate Alterations in Molecular Biomarkers in HER2 Neu Positive Metastatic Breast Cancer Together With Assessment of Trastuzumab Use Beyond Progression After Initial Response to Trastuzumab-taxane Based Treatment
ClinicalTrials.gov ID: NCT00885755
Acronym / sponsor ID: MO22004
Conditions: Breast Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: Hoffmann-La RocheIndustry (pharma, biotech, devices)
Study start: 13 Aug 2009 (actual)
Primary completion: 18 Feb 2013 (actual)
Study completion: 18 Feb 2013 (actual)
First posted: 22 Apr 2009 (estimated)
Results: Posted 5 Oct 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
1	Experimental	Drug: Standard taxane therapy, Drug: capecitabine [Xeloda], Drug: trastuzumab [Herceptin]

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

female patients, >=18 years of age;
HER2-positive breast cancer;
al least one metastatic site amenable for core biopsy;
left ventricular ejection fraction >50%.

Key exclusion criteria (4 listed)

prior adjuvant/neoadjuvant Herceptin within past 6 months;
prior adjuvant taxane therapy within past 12 months;
use of chemotherapy, immunotherapy or biological anticancer therapy within past 3 weeks;
known bleeding diatheses.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Standard taxane therapyAs prescribed	Drug	1
capecitabine [Xeloda]1000mg/m2 po bid on days 1-14 of each 3-week cycle (only in patients who have progressed)	Drug	1
trastuzumab [Herceptin]8mg/kg iv loading dose on day 1 of first 3-week cycle, and 6mg/kg iv on day 1 of each subsequent cycle	Drug	1

Primary outcome

Part I: Progression Free Survival (PFS) by Biomarker
Time frame: 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
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) .
Part II: Progression Free Survival (PFS) by Biomarker
Time frame: 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
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.
Part I: Time to Progression (TTP) by Biomarker
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
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).
Part II: TTP by Biomarker
Time frame: 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
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 .
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
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
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.
Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
Time frame: 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
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.

8 secondary outcomes

Part I: TTP in Intent to Treat (ITT) Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I: PFS in ITT Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part II: TTP in Intent to Treat (ITT) Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part II: PFS in ITT Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Overall Survival in Per Protocol Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
Overall Survival in ITT Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
Time frame: 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 and safety

Results posted to the registry on 5 Oct 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A:Trastuzumab+Taxane /Capecitabine (6 Weeks)	31	13
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks	1	1
No Group	1	0

Primary outcome: Part I: Progression Free Survival (PFS) by Biomarker

Time frame: 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. Median (95% Confidence Interval). Unit: months

Measure	Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) n = 27	Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks n = 1
p95 HER2 +ve (n=9,0)	NA (3.384 to NA)	NA (NA to NA)
p95 HER2 -ve (n=15,1)	13.963 (7.261 to 22.407)	1.216 (NA to NA)
IGF1R <median (n=12,0)	12.649 (4.698 to NA)	NA (NA to NA)
IGF1R ≥median (n=14,1)	22.209 (7.261 to NA)	1.216 (NA to NA)
c-MET <median (n=10,1)	18.595 (3.384 to NA)	1.216 (NA to NA)
c-MET ≥median (n=15,0)	13.733 (7.031 to NA)	NA (NA to NA)
PTEN <median (n=12,0)	22.209 (5.914 to NA)	NA (NA to NA)
PTEN ≥median (n=14,1)	13.963 (6.374 to 31.179)	1.216 (NA to NA)

Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 0.41 (95% CI 0.109 to 1.535)
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 1.19 (95% CI 0.430 to 3.282)
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 0.86 (95% CI 0.306 to 2.425)

Population analysed: 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.

Primary outcome: Part II: Progression Free Survival (PFS) by Biomarker

Time frame: 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. Median (95% Confidence Interval). Unit: months

Measure	Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) n = 27	Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks n = 1
p95 +ve (n=2,0)	8.148 (NA to NA)	NA (NA to NA)
p95 -ve (n=5,1)	3.450 (0.854 to 8.115)	13.832 (NA to NA)
IGF1R <median (n=4,0)	8.115 (0.854 to 8.115)	NA (NA to NA)
IGF1R ≥median (n=4,1)	4.074 (1.971 to 8.148)	13.832 (NA to NA)
c-MET<median (n=3,1)	4.698 (3.450 to 4.698)	13.832 (NA to NA)
c-MET≥median (n=4,0)	5.043 (0.854 to 8.148)	NA (NA to NA)
PTEN <median (n=4,0)	4.698 (1.971 to 8.115)	NA (NA to NA)
PTEN ≥median (n=3,1)	3.450 (0.854 to 8.148)	13.832 (NA to NA)

Population analysed: PP population; n = number of participants with biomarker data available for the specified biomarker.

Primary outcome: Part I: Time to Progression (TTP) by Biomarker

Time frame: End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks. Median (95% Confidence Interval). Unit: months

Measure	Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) n = 27	Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks n = 1
p95 +ve (n=9,0)	NA (3.384 to NA)	NA (NA to NA)
p95 -ve (n=15,1)	13.963 (7.261 to 22.407)	1.216 (NA to NA)
IGF1R <median (n=12,0)	11.335 (4.698 to NA)	NA (NA to NA)
IGF1R ≥median (n=14,1)	22.407 (5.914 to NA)	1.216 (NA to NA)
c-MET <median (n=10,1)	31.179 (3.384 to NA)	1.216 (NA to NA)
c-MET ≥median (n=15,0)	22.209 (6.374 to NA)	NA (NA to NA)
PTEN <median (n=12,0)	22.209 (5.914 to NA)	NA (NA to NA)
PTEN ≥median (n=14,1)	13.963 (6.374 to 31.179)	1.216 (NA to NA)

Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 0.46 (95% CI 0.120 to 1.790)
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 1.18 (95% CI 0.394 to 3.518)
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks): Hazard Ratio (HR): 0.82 (95% CI 0.268 to 2.514)

Population analysed: PP population; n = number of participants with biomarker data available for the specified biomarker.

Primary outcome: Part II: TTP by Biomarker

Measure	Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) n = 27	Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks n = 1
p95 HER2 +ve (n=2,0)	8.148 (NA to NA)	NA (NA to NA)
p95 HER2 -ve (n=5,1)	3.450 (0.854 to 8.115)	13.832 (NA to NA)
IGF1R <median (n=4,0)	8.115 (0.854 to 8.115)	NA (NA to NA)
IGF1R ≥median (n=4,1)	4.074 (1.971 to 8.148)	13.832 (NA to NA)
c-MET <median (n=3,1)	4.698 (3.450 to 4.698)	13.832 (NA to NA)
c-MET ≥median (n=4,0)	5.043 (0.854 to 8.148)	NA (NA to NA)
PTEN <median (n=4,0)	4.698 (1.971 to 8.115)	NA (NA to NA)
PTEN ≥median (n=3,1)	3.450 (0.854 to 8.148)	13.832 (NA to NA)

Population analysed: PP population; n = number of participants with biomarker data available for the specified biomarker.

8 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the date of Screening until 4 weeks after the last visit of the participant. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
All Participants	9 of 33 (27.3%)	33 of 33 (100%)	Not reported

Limitations and caveats (from the sponsor): The study was prematurely terminated on December 31, 2012. The end of study follow-up was February 18, 2013.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Breast Cancer

Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingPhase 2
Gene Signatures to Guide HR+MBC Therapy in a Diverse Cohort
Invasive Mammary Carcinoma, Metastatic Breast Cancer
Not yet recruitingObservational study
Comparison of Reliability, Time Cost, and Participant Comfort of Lymphedema Assessments in Upper Extremity
Lymphedema, Upper Extremity Lymphedema
RecruitingPhase 3
A Study of Camrelizumab Plus Chemotherapy in Combination With or Without Famitinib as Neoadjuvant Therapy in Participants With Triple Negative Breast Cancer (BCTOP-T-N01)
TNBC - Triple-Negative Breast Cancer
RecruitingPhase 3
Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial
Anatomic Stage II Breast Cancer AJCC v8, Anatomic Stage IIIA Breast Cancer AJCC v8

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Clinical Trials study director

Hoffmann-La Roche

13 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Standard taxane therapy, capecitabine [Xeloda] and trastuzumab [Herceptin] in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Australia, United Kingdom, Spain, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part I: Progression Free Survival (PFS) by Biomarker (time frame: 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). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00885755.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2018.