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Combination Chemotherapy With or Without Trastuzumab in Treating Women With Metastatic Breast Cancer
This study has been completed.
Study NCT00004888   Information provided by Eastern Cooperative Oncology Group

First Received on March 7, 2000.   Last Updated on October 18, 2011   History of Changes
Results First Received: June 21, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Trastuzumab
Drug: Docetaxel
Drug: PLD

  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
The study was activated on Oct 19, 2000 and closed on Sept 7, 2004. Accrual to Arm II was suspended on April 23, 2002 for a pre-planned interim analysis regarding cardiac safety and resumed on Nov 6, 2002. Study participants all came from ECOG institutions.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Entry on the study requires determination by the Eastern Cooperative Group Pathology Coordinating Office of HER2 expression status in primary breast tissue or site of metastasis. Patients with PS 2 were excluded from further enrollment in both arms as they were found to experience more severe toxicities and more frequent dose reductions.

Reporting Groups
  Description
Arm I: Doxorubicin and Taxotere Patients received PLD 30 mg/m^2 IV followed by docetaxel 60 mg/m^2 IV, one hour after PLD completion, every 3 weeks for a total of 8 cycles. Dexamthasone 8 mg orally twice a day was administered the day before, the day of, and the day following docetaxel. The maximum allowed cumulative dose of PLD was 240 mg/m^2. Pyridoxine 200 mg PO daily started on Day 1 of Cycle 1 and continued daily while the patient was on PLD.
Arm II: Doxorubicin, Taxotere, and Herceptin Patients received the weekly antibody therapy with trastuzumab in addition to the induction chemotherapy with PLD and docetaxel every 3 weeks as outlined for Arm I above for a total of 8 cycles. Trastuzumab was administered 4 mg/kg IV on Day 1, then 2 mg/kg IV weekly.

Participant Flow:   Overall Study
    Arm I: Doxorubicin and Taxotere     Arm II: Doxorubicin, Taxotere, and Herceptin  
STARTED     38 [1]   46 [2]
COMPLETED     27     22  
NOT COMPLETED     11     24  
Adverse Event                 5                 10  
Withdrawal by Subject                 0                 3  
Physician Decision                 1                 1  
Progressive Disease                 4                 9  
Death without progressive disease                 0                 1  
Toxic death                 1                 0  
[1] Of the 41 pts, 3 were ineligible.
[2] Of the 48 pts, 2 were ineligible.



  Baseline Characteristics
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Reporting Groups
  Description
Arm I: Doxorubicin and Taxotere Patients received PLD 30 mg/m^2 IV followed by docetaxel 60 mg/m^2 IV, one hour after PLD completion, every 3 weeks for a total of 8 cycles. Dexamthasone 8 mg orally twice a day was administered the day before, the day of, and the day following docetaxel. The maximum allowed cumulative dose of PLD was 240 mg/m^2. Pyridoxine 200 mg PO daily started on Day 1 of Cycle 1 and continued daily while the patient was on PLD.
Arm II: Doxorubicin, Taxotere, and Herceptin Patients received the weekly antibody therapy with trastuzumab in addition to the induction chemotherapy with PLD and docetaxel every 3 weeks as outlined for Arm I above for a total of 8 cycles. Trastuzumab was administered 4 mg/kg IV on Day 1, then 2 mg/kg IV weekly.

Baseline Measures
    Arm I: Doxorubicin and Taxotere     Arm II: Doxorubicin, Taxotere, and Herceptin     Total  
Number of Participants  
[units: participants]
 		  38     46     84  
Age  
[units: years]
Median ( Full Range ) 		  53  
  ( 33 to 80 )   		  53  
  ( 23 to 80 )   		  53  
  ( 23 to 80 )  
Gender, Customized [1]
[units: participants]
 		     
Female     38     46     84  
[1] All participants are female.



  Outcome Measures
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1.  Primary:   Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event   [ Time Frame: Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy ]
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2.  Primary:   Summary of Left Ventricular Ejection Fraction Values   [ Time Frame: Baseline, after cycle 4, after cycle 8, and 30 or more days after last cycle of induction therapy. ]
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3.  Secondary:   Best Overall Response Using Eastern Cooperative Group Solid Tumor Response Criteria.   [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of Nov 21, 2007 is used for this report. Please note that best overall response is reported in the table. ]
  Show Outcome Measure 3

4.  Secondary:   Overall Survival   [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report. ]
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5.  Secondary:   Progression-Free Survival   [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report. ]
  Show Outcome Measure 5


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Study Statistician
Organization: Eastern Cooperative Oncology Group Statistical Office
phone: 617-632-3012


Publications of Results:
Wolff AC, Wang M, Sparano JA, et al.: Cardiac safety and clinical activity of pegylated liposomal doxorubicin (D) and docetaxel (T) with and without trastuzumab (H) as 1st line chemotherapy in HER2-positive and HER2-negative metastatic breast cancer (MBC): Eastern Cooperative Oncology Group (ECOG) trial E3198. [Abstract] Breast Cancer Res Treat 88 (Suppl 1): A-3040, 2004.
Wolff AC, Bonetti M, Sparano JA, et al.: Cardiac safety of trastuzumab (H) in combination with pegylated liposomal doxorubicin (D) and docetaxel (T) in HER2-positive metastatic breast cancer (MBC): preliminary results of the Eastern Cooperative Oncology Group trial E3198. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-70, 2003.


Responsible Party: Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00004888     History of Changes
Other Study ID Numbers: CDR0000067564, E3198, U10CA021115
Study First Received: March 7, 2000
Results First Received: June 21, 2011
Last Updated: October 18, 2011
Health Authority: United States: Federal Government





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