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A Study of Trastuzumab Emtansine, Paclitaxel, and Pertuzumab in Patients With HER2-Positive, Locally Advanced or Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00951665
Recruitment Status : Completed
First Posted : August 4, 2009
Results First Posted : June 24, 2016
Last Update Posted : June 24, 2016
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: paclitaxel
Drug: pertuzumab [Perjeta]
Drug: trastuzumab emtansine [Kadcyla]

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted from 21 Jul 2009 to 04 Jun 2013 at 5 centers (4 centers for Phase Ib and 5 centers for Phase IIa) in the United States.

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
Phase Ib Regimen 1 Participants received trastuzumab emtansine (T-DM1) every three weeks (Q3W) + paclitaxel weekly (QW) intravenously.
Phase Ib Regimen 2 Participants received T-DM1 Q3W + paclitaxel QW + pertuzumab Q3W intravenously.
Phase Ib Regimen 3 Participants received T-DM1 QW + paclitaxel QW intravenously.
Phase Ib Regimen 4 Participants received T-DM1 QW + paclitaxel QW + pertuzumab Q3W intravenously.
Phase IIa Group A Participants received maximum tolerated dose (MTD) from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW intravenously.
Phase IIa Group B Participants received T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW + pertuzumab Q3W intravenously.

Participant Flow for 2 periods

 Period 1:   Phase 1b
    Phase Ib Regimen 1   Phase Ib Regimen 2   Phase Ib Regimen 3   Phase Ib Regimen 4   Phase IIa Group A   Phase IIa Group B
STARTED   29   10   21   3   0   0 
Started Treatment   26   10   21   3   0   0 
COMPLETED   7   6   4   2   0   0 
NOT COMPLETED   22   4   17   1   0   0 
Adverse Event                2                1                0                1                0                0 
Death                1                0                2                0                0                0 
Physician Decision                4                0                1                0                0                0 
Withdrawal by Subject                0                1                0                0                0                0 
Disease Progression                13                2                14                0                0                0 
Protocol Violation                2                0                0                0                0                0 

Period 2:   Phase 2a
    Phase Ib Regimen 1   Phase Ib Regimen 2   Phase Ib Regimen 3   Phase Ib Regimen 4   Phase IIa Group A   Phase IIa Group B
STARTED   0   0   0   0   22   22 
COMPLETED   0   0   0   0   10   15 
NOT COMPLETED   0   0   0   0   12   7 
Adverse Event                0                0                0                0                2                0 
Death                0                0                0                0                1                1 
Lost to Follow-up                0                0                0                0                1                0 
Physician Decision                0                0                0                0                0                1 
Withdrawal by Subject                0                0                0                0                2                0 
Disease Progression                0                0                0                0                6                5 



  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.
No text entered.

Reporting Groups
  Description
Phase Ib Regimen 1 Participants received T-DM1 Q3W + paclitaxel QW intravenously.
Phase Ib Regimen 2 Participants received T-DM1 Q3W + paclitaxel QW + pertuzumab Q3W intravenously.
Phase Ib Regimen 3 Participants received T-DM1 QW + paclitaxel QW intravenously.
Phase Ib Regimen 4 Participants received T-DM1 QW + paclitaxel QW + pertuzumab Q3W intravenously.
Phase IIa Group A Participants received MTD from Phase 1b i.e. T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW intravenously.
Phase IIa Group B Participants received T-DM1 3.6mg/kg Q3W + paclitaxel 80mg/m^2 QW + pertuzumab Q3W intravenously.
Total Total of all reporting groups

Baseline Measures
   Phase Ib Regimen 1   Phase Ib Regimen 2   Phase Ib Regimen 3   Phase Ib Regimen 4   Phase IIa Group A   Phase IIa Group B   Total 
Overall Participants Analyzed 
[Units: Participants]
 		 26   10   21   3   22   22   104 
Age 
[Units: Years]
Mean (Standard Deviation) 		 53.3  (12.3)   51.3  (11.9)   54.1  (8.5)   49.3  (4.0)   51.7  (11.8)   55.1  (7.7)   53.2  (10.3) 
Gender 
[Units: Participants]
 		             
Female   26   10   19   3   21   22   101 
Male   0   0   2   0   1   0   3 


  Outcome Measures

1.  Primary:   Number of Participants With Any Adverse Events (AEs), Serious Adverse Events (SAEs), AEs of Grades 3/4, and Death   [ Time Frame: Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later ]
  Show Outcome Measure 1

2.  Primary:   Number of Participants With Dose Limiting Toxicity (DLT) of the Combination of T-DM1 and Paclitaxel When T-DM1 Was Administered on Either an Q3W or QW Schedule for Both With and Without Pertuzumab Treatment   [ Time Frame: Up to 23 days ]
  Show Outcome Measure 2

3.  Primary:   Maximum Tolerated Dose of T-DM1 When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab   [ Time Frame: Days 1 to 21 ]
  Show Outcome Measure 3

4.  Primary:   Maximum Tolerated Dose of Paclitaxel When T-DM1 (Q3W or QW) and Paclitaxel (QW) Was Administered With and Without Pertuzumab   [ Time Frame: Days 1 to 21 ]
  Show Outcome Measure 4

5.  Primary:   Number of Participants in Phase IIa of the Study Who Received 12 or More Paclitaxel Doses in Combination With T-DM1 and/or Pertuzumab   [ Time Frame: From Day 1 to 15 weeks ]
  Show Outcome Measure 5

6.  Primary:   Number of Participants Who Had Adverse Events That Required Dose Modification of T-DM1 or Paclitaxel   [ Time Frame: Up to 30 days after the last dose of study treatment or study discontinuation/termination, whichever is later ]
  Show Outcome Measure 6

7.  Primary:   Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen   [ Time Frame: Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion) ]
  Show Outcome Measure 7

8.  Primary:   Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After Q3W Dose Regimen   [ Time Frame: Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion) ]
  Show Outcome Measure 8

9.  Primary:   Area Under the Serum Concentration-time Curve of Total Exposure (AUC0-Day 21) of T-DM1 and Total Trastuzumab in Cycle 1 After Q3W Dose Regimen   [ Time Frame: Pre- and post-dose (0.25 and 4 hours and Day 8 [before paclitaxel infusion) for Cycle 1 and pre- and post-dose (0.25 and 4 hours) for Cycle 2 (each cycle of 21 days) ]
  Show Outcome Measure 9

10.  Primary:   Maximum Serum Concentration (Cmax) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen   [ Time Frame: Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before paclitaxel infusion) ]
  Show Outcome Measure 10

11.  Primary:   Maximum Plasma Concentration (Cmax) of DM1 in Cycle 1 After QW Dose Regimen   [ Time Frame: Pre-dose, and 0.25 and 4 hours post-dose on Day 1, and Day 8 (before T-DM1 dose) ]
  Show Outcome Measure 11

12.  Primary:   Area Under the Serum Concentration-time Curve of Total Exposure (AUClast) of T-DM1 and Total Trastuzumab in Cycle 1 After QW Dose Regimen   [ Time Frame: Pre-dose, and 0.25 and 4 hours post-dose on Day 1; Day 8 (before T-DM1 dose) ]
  Show Outcome Measure 12

13.  Primary:   Maximum Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence T-DM1) and Cycle 2 (in the Presence T-DM1)   [ Time Frame: Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2 ]
  Show Outcome Measure 13

14.  Primary:   Area Under Plasma Concentration - Time Curve of Paclitaxel From Time 0 to Infinity (AUC0-inf) in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)   [ Time Frame: Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2 ]
  Show Outcome Measure 14

15.  Primary:   An Elimination Half-life (t1/2) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)   [ Time Frame: Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2 ]
  Show Outcome Measure 15

16.  Primary:   Plasma Clearance (CL) of Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)   [ Time Frame: Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2 ]
  Show Outcome Measure 16

17.  Primary:   An Apparent Volume of Distribution at Steady-state (Vss) of Plasma Concentration of Paclitaxel in Cycle 1 (in the Absence of T-DM1) and Cycle 2 (in the Presence of T-DM1)   [ Time Frame: Pre-dose, and 0.25, 1, 2, 4, 6, and 24 hours post-dose for Cycle 1 and Cycle 2 ]
  Show Outcome Measure 17

18.  Primary:   Number of Participants With Change From Baseline in Cardiac Function   [ Time Frame: Baseline (30 days prior to study dose), end of Cycle 2, and then every three cycles in Phase Ib and every four cycles in Phase IIa throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first ]
  Show Outcome Measure 18

19.  Secondary:   Percentage of Participants With Objective Response Rate (ORR)   [ Time Frame: Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first ]
  Show Outcome Measure 19

20.  Secondary:   Duration of Objective Response   [ Time Frame: Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first ]
  Show Outcome Measure 20

21.  Secondary:   Percentage of Participants With Clinical Benefit   [ Time Frame: Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first ]
  Show Outcome Measure 21

22.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: Tumor assessments performed at the end of Cycle 2 and then every 2 cycles (i.e., Cycles 4, 6, 8, 10, etc. [each cycle of 21 days]) throughout the duration of the study (12 months) until disease progression or study discontinuation, whichever occurs first ]
  Show Outcome Measure 22


  Serious Adverse Events


  Other Adverse Events


  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
Given the small sample size in the different patient subsets, no formal hypothesis testing was performed, and all statistical analyses should be considered descriptive and hypothesis-generating only.


  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:
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: Roche Trial Information Hotline
Organization: F. Hoffmann-La Roche AG
phone: +41 61 6878333
e-mail: global.trial_information@roche.com


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


Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00951665     History of Changes
Other Study ID Numbers: TDM4652g
GO01355 ( Other Identifier: Hoffmann-La Roche )
First Submitted: August 3, 2009
First Posted: August 4, 2009
Results First Submitted: January 4, 2016
Results First Posted: June 24, 2016
Last Update Posted: June 24, 2016