Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Study of Pertuzumab in Combination With Herceptin in Patients With HER2 Positive Breast Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00545688
First received: October 16, 2007
Last updated: September 1, 2016
Last verified: September 2016
Results First Received: December 16, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: Herceptin
Drug: docetaxel
Drug: pertuzumab

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 107, 107, 107, and 96 participants (total 417) were randomized to Arms Trastuzumab plus (+) Docetaxel (T+ D) , Trastuzumab+Pertuzumab+Docetaxel (T+Ptz+D), Trastuzumab+Pertuzumab (T+Ptz), and Pertuzumab+Docetaxel (Ptz+D), respectively and were included in intent-to-treat population (as randomized).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
3 participants did not receive correct treatment, as randomized, and 1 (in Arm Trastuzumab + Docetaxel) did not receive any treatment. Safety population (as treated) included 107, 107, 108, and 94 participants in Arms ‘T+D’, ‘T+Ptz+D’, ‘T+Ptz’, and ‘Ptz+D’, respectively. Participant flow was available for “As Treated” participants.

Reporting Groups
  Description
Trastuzumab + Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab intravenous (IV) infusion at a loading dose of 8 milligrams per kilogram (mg/kg) on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 milligrams per square meter (mg/m^2) on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by 5-fluorouracil 600 mg/m^2 IV, epirubicin 90 mg/m^2 IV, and cyclophosphamide 600 mg/m^2 IV (FEC) on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Trastuzumab+Pertuzumab+Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Trastuzumab+Pertuzumab

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Pertuzumab+Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.


Participant Flow for 3 periods

Period 1:   Neo-Adjuvant Treatment Period
    Trastuzumab + Docetaxel   Trastuzumab+Pertuzumab+Docetaxel   Trastuzumab+Pertuzumab   Pertuzumab+Docetaxel
STARTED   107   107   108   94 
COMPLETED   103   102   94   88 
NOT COMPLETED   4   5   14   6 
Protocol Violation                1                2                1                1 
Refused Treatment                1                1                4                1 
Lost to Follow-up                1                0                0                0 
Death                0                1                0                0 
Disease Progression                0                1                7                2 
Unknown Reason                1                0                0                0 
Adverse Event                0                0                2                2 

Period 2:   Adjuvant Treatment Period
    Trastuzumab + Docetaxel   Trastuzumab+Pertuzumab+Docetaxel   Trastuzumab+Pertuzumab   Pertuzumab+Docetaxel
STARTED   103   102   94   88 
COMPLETED   98   94   90   74 
NOT COMPLETED   5   8   4   14 
Disease Progression                3                3                0                7 
Refused Treatment                1                1                1                5 
Lost to Follow-up                1                0                1                0 
Adverse Event                0                3                2                2 
Unknown Reason                0                1                0                0 

Period 3:   Follow-Up Period
    Trastuzumab + Docetaxel   Trastuzumab+Pertuzumab+Docetaxel   Trastuzumab+Pertuzumab   Pertuzumab+Docetaxel
STARTED   98   102   98   87 
COMPLETED   77   83   78   60 
NOT COMPLETED   21   19   20   27 
Death                4                2                2                6 
Disease Progression                6                5                9                9 
Refused Treatment                6                2                0                2 
Lost to Follow-up                3                3                3                1 
Unspecified Reason                2                5                6                8 
Violation of Selection Criteria at Entry                0                2                0                1 



  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.
Intent-To-Treat (ITT) Population included all randomized participants who received any amount of study medication. Analysis was performed according to initial randomization.

Reporting Groups
  Description
Trastuzumab+Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg on Day 1 of Cycles 2-4 and docetaxel IV infusion at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Trastuzumab+Pertuzumab+Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 17.

Trastuzumab+Pertuzumab

Neoadjuvant (Pre-Operative) Treatment: Participants received trastuzumab IV infusion at a loading dose of 8 mg/kg and pertuzumab IV infusion at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 6 mg/kg trastuzumab and 420 mg pertuzumab on Day 1 of Cycles 2-4.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by docetaxel 75 mg/m^2 IV on Day 1 of Cycle 5 followed by docetaxel 100 mg/m^2 for three cycles (Cycles 6−8) if no dose-limiting toxicity occurred. For Cycles 9 to 11, participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles. Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 12 until Cycle 17.

Pertuzumab+Docetaxel

Neoadjuvant (Pre-Operative) Treatment: Participants received pertuzumab IV at a loading dose of 840 mg on Day 1 of Cycle 1 (21-day cycle) followed by a maintenance dose of 420 mg on Day 1 of Cycles 2-4. Docetaxel IV infusion was administered at a starting dose of 75 mg/m^2 on Day 1 of Cycle 1 followed by 100 mg/m^2 on Day 1 of Cycles 2-4, if no dose limiting toxicity occurred.

Adjuvant (2-Week Post-Operative) Treatment: Participants received trastuzumab 6 mg/kg IV followed by FEC on Day 1 and every 3 weeks thereafter for three cycles (Cycles 5−7). Trastuzumab 6 mg/kg IV was continued every 3 weeks from Cycle 8 to Cycle 21.

Total Total of all reporting groups

Baseline Measures
   Trastuzumab+Docetaxel   Trastuzumab+Pertuzumab+Docetaxel   Trastuzumab+Pertuzumab   Pertuzumab+Docetaxel   Total 
Overall Participants Analyzed 
[Units: Participants]
 107   107   107   96   417 
Age 
[Units: Years]
Mean (Standard Deviation)
 50.9  (8.94)   49.6  (10.05)   49.7  (10.67)   48.9  (10.50)   49.8  (10.04) 
Gender 
[Units: Participants]
         
Female   107   107   107   96   417 
Male   0   0   0   0   0 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Achieving Pathological Complete Response (pCR)   [ Time Frame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4) ]

2.  Primary:   Percentage of Participants Achieving pCR by Breast Cancer Type   [ Time Frame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4) ]

3.  Primary:   Percentage of Participants Achieving pCR by Hormone Receptor Status   [ Time Frame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4) ]

4.  Primary:   Percentage of Participants Achieving pCR by Lymph Node Status   [ Time Frame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4) ]

5.  Primary:   Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)   [ Time Frame: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4) ]

6.  Secondary:   Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography   [ Time Frame: Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

7.  Secondary:   Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

8.  Secondary:   Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

9.  Secondary:   Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

10.  Secondary:   Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

11.  Secondary:   Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

12.  Secondary:   Time to Clinical Response During Neo-Adjuvant Treatment Period   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

13.  Secondary:   Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period   [ Time Frame: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months ]

14.  Secondary:   Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned   [ Time Frame: Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months ]

15.  Secondary:   Percentage of Participants Who Were Progression Free and Disease Free   [ Time Frame: Randomization up to a maximum of 329 weeks ]

16.  Secondary:   Progression Free and Disease Free Survival   [ Time Frame: Randomization up to a maximum of 329 weeks ]


  Serious Adverse Events


  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:
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: Hoffmannb-LaRoche
phone: 1-800-821-8590
e-mail: genentech@druginfo.com


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

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00545688     History of Changes
Other Study ID Numbers: WO20697
Study First Received: October 16, 2007
Results First Received: December 16, 2015
Last Updated: September 1, 2016
Health Authority: Italy: AIFA (Agenzia Italiana Farmaco)