A Study of Trastuzumab-MCC-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer Who Have Previously Received a Trastuzumab-Containing Regimen

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00932373
First received: June 30, 2009
Last updated: August 13, 2015
Last verified: August 2015
Results First Received: July 1, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Intervention: Drug: trastuzumab-MCC-DM1

  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
Approximately four centers in the United States were to participate in the study to enroll approximately 50-60 patients. Between 25 April 2006 and 20 May 2008, 54 patients were enrolled and 52 were treated.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Two patients enrolled but discontinued the study prior to receiving study treatment drug, thus 52 patients received at least one dose and are included in the baseline and safety analysis data.

Reporting Groups
  Description
Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week

Participant Flow:   Overall Study
    Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 1.2 mg/kg Weekly     Trastuzumab-MCC-DM1 1.6 mg/kg Weekly     Trastuzumab-MCC-DM1 2.0 mg/kg Weekly     Trastuzumab-MCC-DM1 2.4 mg/kg Weekly     Trastuzumab-MCC-DM1 2.9 mg/kg Weekly  
STARTED     3     1     1     1     15     3     3     3     3     16     3  
COMPLETED     0     0     0     1     1     0     2     0     1     3     0  
NOT COMPLETED     3     1     1     0     14     3     1     3     2     13     3  
Progressive disease                 3                 1                 0                 0                 10                 1                 0                 2                 1                 9                 2  
Adverse Event                 0                 0                 0                 0                 2                 1                 0                 1                 0                 2                 1  
Physician Decision                 0                 0                 1                 0                 2                 0                 0                 0                 0                 1                 0  
Dose limiting toxicity                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0                 0  
Withdrawal by Subject                 0                 0                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Clinical progression                 0                 0                 0                 0                 0                 0                 1                 0                 0                 0                 0  
Lack of Efficacy                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 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.
All summaries were based on data from the safety population (patients who received at least one dose of Trastuzumab-MCC-DM1). All summaries were presented for all patients and by dose level and schedule.

Reporting Groups
  Description
Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks
Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week
Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week
Total Total of all reporting groups

Baseline Measures
    Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks     Trastuzumab-MCC-DM1 1.2 mg/kg Weekly     Trastuzumab-MCC-DM1 1.6 mg/kg Weekly     Trastuzumab-MCC-DM1 2.0 mg/kg Weekly     Trastuzumab-MCC-DM1 2.4 mg/kg Weekly     Trastuzumab-MCC-DM1 2.9 mg/kg Weekly     Total  
Number of Participants  
[units: participants]
  3     1     1     1     15     3     3     3     3     16     3     52  
Age  
[units: Years]
Mean (Standard Deviation)
  60.7  (10.1)     47.0  (0)     61.0  (0)     58.0  (0)     52.1  (10.3)     48.0  (6.0)     55.3  (10.0)     53.0  (6.1)     55.3  (3.2)     50.9  (14.0)     58.3  (11.0)     52.9  (10.7)  
Gender  
[units: participants]
                       
Female     3     1     1     1     15     3     3     3     3     16     3     52  
Male     0     0     0     0     0     0     0     0     0     0     0     0  
Region of Enrollment  
[units: participants]
                       
United States     3     1     1     1     15     3     3     3     3     16     3     52  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment   [ Time Frame: Study treatment initiation until 30 or 90 days after last administration of study treatment ]

2.  Primary:   Number of Patients With Dose Limiting Toxicities (DLTs)   [ Time Frame: A minimum of 21 days after first dose of trastuzumab-MCC-DM1 ]

3.  Primary:   Maximum Tolerated Dose (MTD)   [ Time Frame: A minimum of 21 days after first dose of trastuzumab-MCC-DM1 ]

4.  Primary:   Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations   [ Time Frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 ]

5.  Primary:   PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations   [ Time Frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 ]

6.  Primary:   PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations   [ Time Frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 ]

7.  Secondary:   Percentage of Participants With an Objective Response   [ Time Frame: Baseline to the end of the study (up to 3 years 2 months) ]

8.  Secondary:   Duration of Objective Response   [ Time Frame: Baseline to the end of the study (up to 3 years 2 months) ]

9.  Secondary:   Progression-free Survival   [ Time Frame: Baseline to the end of the study (up to 3 years 2 months) ]

10.  Secondary:   Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine   [ Time Frame: Baseline to the end of the study (up to 3 years 2 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
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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 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: Genentech, Inc.
phone: 800 821-8590
e-mail: genentech@druginfo.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00932373     History of Changes
Other Study ID Numbers: TDM3569g
Study First Received: June 30, 2009
Results First Received: July 1, 2015
Last Updated: August 13, 2015
Health Authority: United States: Food and Drug Administration