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A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01120184
First Posted: May 10, 2010
Last Update Posted: November 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Hoffmann-La Roche
Results First Submitted: May 2, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Breast Cancer
Interventions: Drug: docetaxel
Drug: paclitaxel
Drug: pertuzumab
Drug: pertuzumab-placebo
Drug: trastuzumab [Herceptin]
Drug: trastuzumab emtansine

  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
No text entered.

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
Trastuzumab + Taxane Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.

Participant Flow:   Overall Study
    Trastuzumab + Taxane   Trastuzumab Emtansine + Placebo   Trastuzumab Emtansine + Pertuzumab
STARTED   365   367   363 
Treated   355   365   360 
COMPLETED   0   0   0 
NOT COMPLETED   365   367   363 
Adverse Event                0                1                0 
Lost to Follow-up                13                13                11 
Physician Decision                9                1                3 
Reason not Specified                8                3                12 
Sponsor Decision to Terminate Study                133                144                143 
Subject/ Guardian Decision to Withdraw                32                29                25 
Death                170                176                169 



  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.
Intent-to-Treat (ITT) Population: All participants randomized in the study.

Reporting Groups
  Description
Trastuzumab + Taxane Participants received trastuzumab plus either docetaxel or paclitaxel. The regimen was chosen at the investigator's discretion. Option 1: trastuzumab 8 mg/kg via IV infusion on Day 1 of Cycle 1, then 6 mg/kg IV on Day 1 of each subsequent 3-week cycle; plus a minimum of 6 cycles with docetaxel 75 or 100 mg/m^2 IV on Day 1 of each 3-week cycle. Option 2: trastuzumab 4 mg/kg IV on Day 1 of Cycle 1, then 2 mg/kg IV weekly beginning on Day 8 of Cycle 1; plus a minimum of 18 weeks with paclitaxel 80 mg/m^2 IV weekly. Treatment continued until disease progression, unacceptable toxicity, or study termination. If trastuzumab or docetaxel were discontinued for toxicity, the other agent could be continued as monotherapy.
Trastuzumab Emtansine + Placebo Participants received trastuzumab emtansine plus pertuzumab-placebo. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the placebo IV infusion, on Day 1 of each 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Trastuzumab Emtansine + Pertuzumab Participants received trastuzumab emtansine plus pertuzumab. Trastuzumab emtansine was administered as 3.6 mg/kg via IV infusion, following completion of the pertuzumab IV infusion, on Day 1 of each 3-week cycle. Pertuzumab was given as 840 mg IV on Day 1 of Cycle 1, then 420 mg IV on Day 1 of each subsequent 3-week cycle. Treatment continued until disease progression, unacceptable toxicity, or study termination.
Total Total of all reporting groups

Baseline Measures
   Trastuzumab + Taxane   Trastuzumab Emtansine + Placebo   Trastuzumab Emtansine + Pertuzumab   Total 
Overall Participants Analyzed 
[Units: Participants]
 365   367   363   1095 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.2  (11.3)   52.6  (11.4)   52.2  (12.0)   53.0  (11.6) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      362  99.2%      365  99.5%      361  99.4%      1088  99.4% 
Male      3   0.8%      2   0.5%      2   0.6%      7   0.6% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

2.  Primary:   Progression-Free Survival (PFS) According to IRF Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

3.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

4.  Secondary:   Overall Survival (OS) at Clinical Cutoff   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

5.  Secondary:   Percentage of Participants With Death or Disease Progression According to Investigator Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

6.  Secondary:   PFS According to Investigator Assessment   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

7.  Secondary:   Percentage of Participants Experiencing Treatment Failure   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

8.  Secondary:   Time to Treatment Failure (TTF)   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

9.  Secondary:   One-Year Survival Rate   [ Time Frame: From randomization until 1 year ]

10.  Secondary:   Percentage of Participants With Grade ≥3 Adverse Events   [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose ]

11.  Secondary:   Percentage of Participants Who Died at 2 Years   [ Time Frame: From randomization until 2 years ]

12.  Secondary:   Overall Survival Truncated at 2 Years   [ Time Frame: From randomization until 2 years ]

13.  Secondary:   Percentage of Participants With Grade 5 Adverse Events   [ Time Frame: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose) ]

14.  Secondary:   Percentage of Participants With Grade 3-4 Laboratory Parameters   [ Time Frame: Day 1, 8, and 15 of Cycle 1–3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014 ]

15.  Secondary:   Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status   [ Time Frame: Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months) ]

16.  Secondary:   Hospitalization Days   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

17.  Secondary:   Percentage of Participants With Hospitalization   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 ]

18.  Secondary:   Percentage of Participants With Objective Response According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

19.  Secondary:   Percentage of Participants With Objective Response According to Investigator Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

20.  Secondary:   Duration of Response According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

21.  Secondary:   Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

22.  Secondary:   Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score   [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

23.  Secondary:   Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module   [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

24.  Secondary:   Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module   [ Time Frame: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2 ]

25.  Secondary:   Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score   [ Time Frame: Up to 39 months from randomization until clinical cutoff of 16-Sept-2014 (at Baseline, on Day 1 of Cycles 2 to 8 and every even-numbered cycle thereafter and/or up to 42 days after last dose) ]

26.  Secondary:   Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score   [ Time Frame: Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014 ]

27.  Secondary:   Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

28.  Secondary:   Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

29.  Secondary:   Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score   [ Time Frame: Baseline, Cycle 7 (Week 18) ]

30.  Secondary:   Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

31.  Secondary:   Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

32.  Secondary:   Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

33.  Secondary:   PFS According to IRF Assessment Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

34.  Secondary:   Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

35.  Secondary:   PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose) ]

36.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

37.  Secondary:   OS at Clinical Cutoff Among Those With High HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

38.  Secondary:   Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]

39.  Secondary:   OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels   [ Time Frame: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats


  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: Hoffmann-La Roche
phone: 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: NCT01120184     History of Changes
Other Study ID Numbers: BO22589
2009-017905-13 ( EudraCT Number )
First Submitted: April 28, 2010
First Posted: May 10, 2010
Results First Submitted: May 2, 2016
Results First Posted: February 23, 2017
Last Update Posted: November 7, 2017