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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00885755
Registration number
NCT00885755
Ethics application status
Date submitted
16/03/2009
Date registered
22/04/2009
Date last updated
29/03/2018
Titles & IDs
Public title
A Study of Herceptin (Trastuzumab)and Biomarkers in Patients With HER2-Positive Metastatic Breast Cancer
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Scientific 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
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Secondary ID [1]
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2008-004013-94
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Secondary ID [2]
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MO22004
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Breast Cancer
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Condition category
Condition code
Cancer
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Breast
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Standard taxane therapy
Treatment: Drugs - capecitabine [Xeloda]
Treatment: Drugs - trastuzumab [Herceptin]
Experimental: 1 -
Treatment: Drugs: Standard taxane therapy
As prescribed
Treatment: Drugs: capecitabine [Xeloda]
1000mg/m2 po bid on days 1-14 of each 3-week cycle (only in patients who have progressed)
Treatment: Drugs: 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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Part I: Progression Free Survival (PFS) by Biomarker
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Assessment method [1]
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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) .
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Timepoint [1]
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End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Primary outcome [2]
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Part II: Progression Free Survival (PFS) by Biomarker
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Assessment method [2]
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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.
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Timepoint [2]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Primary outcome [3]
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Part I: Time to Progression (TTP) by Biomarker
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Assessment method [3]
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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).
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Timepoint [3]
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End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
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Primary outcome [4]
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Part II: TTP by Biomarker
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Assessment method [4]
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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 .
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Timepoint [4]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Primary outcome [5]
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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
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Assessment method [5]
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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.
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Timepoint [5]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 weeks
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Primary outcome [6]
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Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
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Assessment method [6]
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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.
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Timepoint [6]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [1]
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Part I: TTP in Intent to Treat (ITT) Population
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Assessment method [1]
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TTP was determined as the time in months from the date of screening until first progression. In participants with measurable disease, progression was defined according to RECIST (SLD increased by at least 20% from the smallest value on study [including baseline, if that is the smallest]). In participants with non-measurable disease, progression was defined as the presence of new lesions or unequivocal progression during treatment.
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Timepoint [1]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [2]
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Part I: PFS in ITT Population
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Assessment method [2]
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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.
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Timepoint [2]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [3]
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Part II: TTP in Intent to Treat (ITT) Population
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Assessment method [3]
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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.
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Timepoint [3]
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End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [4]
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Part II: PFS in ITT Population
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Assessment method [4]
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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.
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Timepoint [4]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [5]
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Overall Survival in Per Protocol Population
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Assessment method [5]
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Overall survival was calculated in months from the day of screening until death.
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Timepoint [5]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
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Secondary outcome [6]
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Overall Survival in ITT Population
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Assessment method [6]
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Overall survival was calculated in months from the day of screening until death.
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Timepoint [6]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until death (up to 46 months)
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Secondary outcome [7]
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Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
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Assessment method [7]
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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.
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Timepoint [7]
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End of first 2 Cycles (Weeks 3 and 6), every 3 Cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Secondary outcome [8]
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Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
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Assessment method [8]
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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.
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Timepoint [8]
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End of first 2 Cycles (Weeks 3 and 6), every 3 cycles for 18 weeks, then every 4 cycles until progression, unacceptable toxicity or participant decision to cease treatment up to 46 months
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Eligibility
Key inclusion criteria
- female patients, >=18 years of age;
- HER2-positive breast cancer;
- al least one metastatic site amenable for core biopsy;
- left ventricular ejection fraction >50%.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
N/A
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
13/08/2009
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/02/2013
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Sample size
Target
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Accrual to date
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Final
33
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Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
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Recruitment hospital [1]
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Royal Prince Alfred Hospital; Medical Oncology - Camperdown
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Recruitment hospital [2]
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Royal North Shore Hospital; Oncology - St. Leonards
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Recruitment hospital [3]
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Eastern Health Breast Cancer Research - East Ringwood
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Recruitment hospital [4]
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Border Medical Oncology; Murray Valley Private Hospital - Wodonga
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Recruitment hospital [5]
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Mount Medical Center - Perth
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Recruitment hospital [6]
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Royal Perth Hospital; Department of Medical Oncology - Perth
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Recruitment postcode(s) [1]
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2050 - Camperdown
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Recruitment postcode(s) [2]
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2065 - St. Leonards
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Recruitment postcode(s) [3]
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3135 - East Ringwood
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Recruitment postcode(s) [4]
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3690 - Wodonga
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Recruitment postcode(s) [5]
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6000 - Perth
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Recruitment outside Australia
Country [1]
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Spain
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State/province [1]
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Cantabria
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Country [2]
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Spain
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State/province [2]
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Valencia
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Country [3]
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Sweden
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State/province [3]
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Stockholm
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Country [4]
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Sweden
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State/province [4]
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Uppsala
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Country [5]
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United Kingdom
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State/province [5]
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Hull
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Country [6]
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United Kingdom
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State/province [6]
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Manchester
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Country [7]
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United Kingdom
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State/province [7]
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Nottingham
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This single arm study will evaluate alterations in molecular marker expression in
HER2-positive targeted therapy, and will evaluate the effect of continued treatment with
Herceptin and Xeloda beyond progression following initial Herceptin-taxane chemotherapy.
Patients who develop progressive disease will receive first-line Herceptin (8mg/kg iv loading
dose and 6mg/kg iv every 3 weeks) + taxane therapy. patients who develop progressive disease
within 9 weeks of treatment will continue treatment with Herceptin in combination with Xeloda
(1000mg/m2 po bid on days 1-14 of each 3-week cycle).Biopsies of tumor tissue will be taken
for biomarker and gene profiling evaluation. The anticipated time on study treatment is until
disease progression, intolerable side effects or patient choice, and the target sample size
is 100 individuals.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00885755
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Clinical Trials
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Address
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Hoffmann-La Roche
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00885755
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