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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00885755
First received: March 16, 2009
Last updated: July 1, 2016
Last verified: July 2016
Results First Received: September 1, 2015  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Standard taxane therapy
Drug: capecitabine [Xeloda]
Drug: trastuzumab [Herceptin]

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
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.

Participant Flow for 2 periods

Period 1:   Part I: Trastuzumab+Taxane
    Group A:Trastuzumab+Taxane /Capecitabine (6 Weeks)     Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks     No Group  
STARTED     31     1     1  
COMPLETED     13     1     0  
NOT COMPLETED     18     0     1  
Adverse Event                 1                 0                 0  
Unknown Reason                 16                 0                 0  
Sufficient Response Achieved                 1                 0                 0  
Death                 0                 0                 1  

Period 2:   Part II: Trastuzumab + Capecitabine.
    Group A:Trastuzumab+Taxane /Capecitabine (6 Weeks)     Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks     No Group  
STARTED     13     1     0  
COMPLETED     8     1     0  
NOT COMPLETED     5     0     0  
Unknown Reason                 5                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: All registered participants were included in the ITT population.

Reporting Groups
  Description
Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks) This group included participants who progressed after at least six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation.
Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks This group included participants who progressed within less than six weeks of trastuzumab/taxane treatment. In Part I of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression. In Part II of the study, participants received capecitabine twice-daily 1000 mg/m^2 or higher, calculated based on BSA on days 1 to 14 while continuing trastuzumab treatment per standard practice until disease progression, unmanageable toxicity or participant request for discontinuation.
No Group This group included participants who died before any on study disease assessments or post-baseline biopsies. In Part 1 of the study, participants received standard first-line therapy with trastuzumab and, at the discretion of treating clinician, either paclitaxel or docetaxel. Paclitaxel and docetaxel were administered according to one of following regimens: docetaxel 75 mg/m^2 or 100 mg/m^2 3-weekly (if docetaxel-naïve) or docetaxel 75 mg/m^2 3-weekly (if prior adjuvant docetaxel) or docetaxel 60 mg/m^2 3-weekly (if liver dysfunction due to metastatic involvement) or paclitaxel 80 mg/m^2 weekly or 175 mg/m^2 3-weekly until first disease progression.
Total Total of all reporting groups

Baseline Measures
    Group A: Trastuzumab+Taxane /Capecitabine (6 Weeks)     Group B: Trastuzumab+Taxane/ Capecitabine <6 Weeks     No Group     Total  
Number of Participants  
[units: participants]
  31     1     1     33  
Age  
[units: years]
Mean (Standard Deviation)
  55.5  (11.73)     37.0 [1]   85.0 [1]   55.9  (12.91)  
Gender  
[units: participants]
       
Female     31     1     1     33  
Male     0     0     0     0  
[1] Standard deviation was not available since there was only 1 participant.



  Outcome Measures
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1.  Primary:   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 ]

2.  Primary:   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 ]

3.  Primary:   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 ]

4.  Primary:   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 ]

5.  Primary:   Part I: Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progrerssive Disease (PD) by Biomarker   [ 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 ]

6.  Primary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   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) ]

12.  Secondary:   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) ]

13.  Secondary:   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 ]

14.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was prematurely terminated on December 31, 2012. The end of study follow-up was February 18, 2013.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Hoffmann-La Roche
phone: 800-821-8590
e-mail: genentech@druginfo.com



Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00885755     History of Changes
Other Study ID Numbers: MO22004
2008-004013-94
Study First Received: March 16, 2009
Results First Received: September 1, 2015
Last Updated: July 1, 2016
Health Authority: Australia: National Health and Medical Research Council