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

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

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

Hide Baseline Characteristics

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 ]

Show Outcome Measure 1

2. Primary:

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

Show Outcome Measure 2

3. Primary:

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

Show Outcome Measure 3

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 ]

Show Outcome Measure 4

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 ]

Show Outcome Measure 5

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 ]

Show Outcome Measure 6

7. Secondary:

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

Show Outcome Measure 7

8. Secondary:

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

Show Outcome Measure 8

9. Secondary:

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

Show Outcome Measure 9

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) ]

Show Outcome Measure 10

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

Limitations and Caveats

Hide 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.

More Information

Hide More Information

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

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):

Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, Holden SN, Modi S. A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer. Cancer. 2012 Dec 1;118(23):5733-40. doi: 10.1002/cncr.27622. Epub 2012 May 30.

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