Clinical trial NCT00885755: A Study of Herceptin (Trastuzumab)and Biomarkers in Patients With HER2-Positive Metastatic Breast Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2009-04-22
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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%.

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.

Primary outcomes:
measure: Part I: Progression Free Survival (PFS) by Biomarker
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
measure: Part II: Progression Free Survival (PFS) by Biomarker
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
measure: Part I: Time to Progression (TTP) by Biomarker
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 weeks
measure: Part II: TTP by Biomarker
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
measure: 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
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 weeks
measure: Part II: Percentage of Participants With a Best Overall Response of CR, PR, SD or PD by Biomarker
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
Secondary outcomes:
measure: Part I: TTP in Intent to Treat (ITT) Population
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
measure: Part I: PFS in ITT Population
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
measure: Part II: TTP in Intent to Treat (ITT) Population
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
measure: Part II: PFS in ITT Population
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
measure: Overall Survival in Per Protocol Population
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)
measure: Overall Survival in ITT Population
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)
measure: Part I and II: Percentage of Participants With a Best Overall Response of CR or PR in ITT Population
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
measure: Part I and II: Percentage of Participants With a Response by Best Overall Response by CR, PR, SD or PD in ITT Population
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
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital; Medical Oncology
state: New South Wales
city: St. Leonards
country: Australia
facility: Royal North Shore Hospital; Oncology
state: New South Wales
city: East Ringwood
country: Australia
facility: Eastern Health Breast Cancer Research
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology; Murray Valley Private Hospital
state: Victoria
city: Perth
country: Australia
facility: Mount Medical Center
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital; Department of Medical Oncology
state: Western Australia
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
state: Cantabria
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Stockholm
country: Sweden
facility: Karolinska Hospital; Oncology - Radiumhemmet
city: Uppsala
country: Sweden
facility: Akademiska sjukhuset, Onkologkliniken
city: Hull
country: United Kingdom
facility: Hull Royal Infirmary
city: Manchester
country: United Kingdom
facility: Christie Hospital; Breast Cancer Research Office
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital; Oncology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: