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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01120184




Registration number
NCT01120184
Ethics application status
Date submitted
28/04/2010
Date registered
10/05/2010
Date last updated
4/03/2024

Titles & IDs
Public title
A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)
Scientific title
A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
Secondary ID [1] 0 0
2009-017905-13
Secondary ID [2] 0 0
BO22589
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - docetaxel
Treatment: Drugs - paclitaxel
Treatment: Drugs - pertuzumab
Treatment: Drugs - pertuzumab-placebo
Treatment: Drugs - trastuzumab [Herceptin]
Treatment: Drugs - trastuzumab emtansine

Experimental: Trastuzumab + Taxane (docetaxel or paclitaxel) -

Experimental: Trastuzumab emtansine + pertuzumab -

Experimental: Trastuzumab emtansine + pertuzumab placebo -


Treatment: Drugs: docetaxel
75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.

Treatment: Drugs: paclitaxel
80 mg/m2 intravenously weekly for a minimum of 18 weeks

Treatment: Drugs: pertuzumab
840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Treatment: Drugs: pertuzumab-placebo
840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles

Treatment: Drugs: trastuzumab [Herceptin]
trastuzumab \[Herceptin\] doses when administered with docetaxel: 8 mg/kg intravenously on cycle 1 followed by 6 mg/kg every 3 weeks in subsequent cycles or trastuzumab (Herceptin) doses when administered with paclitaxel: 4 mg/kg intravenously on day 1 of cycle 1 followed by 2 mg/kg weekly starting on day 8 of cycle 1.

Treatment: Drugs: trastuzumab emtansine
3.6 mg/kg intravenously every 3 weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
Progression-Free Survival (PFS) According to IRF Assessment
Timepoint [2] 0 0
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)
Secondary outcome [1] 0 0
Percentage of Participants Who Died Prior to Clinical Cutoff
Timepoint [1] 0 0
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)
Secondary outcome [2] 0 0
Overall Survival (OS) at Clinical Cutoff
Timepoint [2] 0 0
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)
Secondary outcome [3] 0 0
Percentage of Participants With Death or Disease Progression According to Investigator Assessment
Timepoint [3] 0 0
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)
Secondary outcome [4] 0 0
PFS According to Investigator Assessment
Timepoint [4] 0 0
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)
Secondary outcome [5] 0 0
Percentage of Participants Experiencing Treatment Failure
Timepoint [5] 0 0
Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Secondary outcome [6] 0 0
Time to Treatment Failure (TTF)
Timepoint [6] 0 0
Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Secondary outcome [7] 0 0
One-Year Survival Rate
Timepoint [7] 0 0
From randomization until 1 year
Secondary outcome [8] 0 0
Percentage of Participants With Grade =3 Adverse Events
Timepoint [8] 0 0
Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose
Secondary outcome [9] 0 0
Percentage of Participants Who Died at 2 Years
Timepoint [9] 0 0
From randomization until 2 years
Secondary outcome [10] 0 0
Overall Survival Truncated at 2 Years
Timepoint [10] 0 0
From randomization until 2 years
Secondary outcome [11] 0 0
Percentage of Participants With Grade 5 Adverse Events
Timepoint [11] 0 0
Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose)
Secondary outcome [12] 0 0
Percentage of Participants With Grade 3-4 Laboratory Parameters
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Percentage of Participants With Decline of =2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Timepoint [13] 0 0
Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months)
Secondary outcome [14] 0 0
Hospitalization Days
Timepoint [14] 0 0
Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Secondary outcome [15] 0 0
Percentage of Participants With Hospitalization
Timepoint [15] 0 0
Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
Secondary outcome [16] 0 0
Percentage of Participants With Objective Response According to IRF Assessment
Timepoint [16] 0 0
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)
Secondary outcome [17] 0 0
Percentage of Participants With Objective Response According to Investigator Assessment
Timepoint [17] 0 0
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)
Secondary outcome [18] 0 0
Duration of Response According to IRF Assessment
Timepoint [18] 0 0
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)
Secondary outcome [19] 0 0
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
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
Timepoint [20] 0 0
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)
Secondary outcome [21] 0 0
Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module
Timepoint [21] 0 0
At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
Secondary outcome [22] 0 0
Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module
Timepoint [22] 0 0
At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
Secondary outcome [23] 0 0
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
Timepoint [23] 0 0
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)
Secondary outcome [24] 0 0
Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score
Timepoint [24] 0 0
Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014
Secondary outcome [25] 0 0
Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score
Timepoint [25] 0 0
Baseline, Cycle 7 (Week 18)
Secondary outcome [26] 0 0
Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
Timepoint [26] 0 0
Baseline, Cycle 7 (Week 18)
Secondary outcome [27] 0 0
Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
Timepoint [27] 0 0
Baseline, Cycle 7 (Week 18)
Secondary outcome [28] 0 0
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
Timepoint [28] 0 0
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)
Secondary outcome [29] 0 0
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels
Timepoint [29] 0 0
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)
Secondary outcome [30] 0 0
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels
Timepoint [30] 0 0
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)
Secondary outcome [31] 0 0
PFS According to IRF Assessment Among Those With High HER2 mRNA Levels
Timepoint [31] 0 0
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)
Secondary outcome [32] 0 0
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels
Timepoint [32] 0 0
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)
Secondary outcome [33] 0 0
PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels
Timepoint [33] 0 0
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)
Secondary outcome [34] 0 0
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels
Timepoint [34] 0 0
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)
Secondary outcome [35] 0 0
OS at Clinical Cutoff Among Those With High HER2 mRNA Levels
Timepoint [35] 0 0
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)
Secondary outcome [36] 0 0
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels
Timepoint [36] 0 0
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)
Secondary outcome [37] 0 0
OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels
Timepoint [37] 0 0
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)

Eligibility
Key inclusion criteria
* Adult participants >/=18 years of age
* HER2-positive breast cancer
* Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease, and be a candidate for chemotherapy. Participants with locally advanced disease must have recurrent or progressive disease, which must not be amenable to resection with curative intent.
* Participants must have measurable and/or non-measurable disease which must be evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Adequate organ function as determined by laboratory results
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* History of prior (or any) chemotherapy for metastatic breast cancer or recurrent locally advanced disease
* An interval of <6 months from the last dose of vinca-alkaloid or taxane cytotoxic chemotherapy until the time of metastatic diagnosis
* Hormone therapy <7 days prior to randomization
* Trastuzumab therapy and/or lapatinib (neo- or adjuvant setting) <21 days prior to randomization
* Prior trastuzumab emtansine or pertuzumab therapy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/07/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/09/2016
Sample size
Target
Accrual to date
Final
1095
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Mater Misericordiae Hospital; Chemotherapy Cottage - Sydney
Recruitment hospital [2] 0 0
Calvary Mater Newcastle; Medical Oncology - Waratah
Recruitment hospital [3] 0 0
Wesley Medical Centre; Clinic For Haematology and Oncology - Auchenflower
Recruitment hospital [4] 0 0
Royal Adelaide Hospital; Oncology - Adelaide
Recruitment hospital [5] 0 0
Peter Maccallum Cancer Institute; Medical Oncology - Melbourne
Recruitment postcode(s) [1] 0 0
2060 - Sydney
Recruitment postcode(s) [2] 0 0
2298 - Waratah
Recruitment postcode(s) [3] 0 0
4066 - Auchenflower
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment postcode(s) [5] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Idaho
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maine
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Massachusetts
Country [14] 0 0
United States of America
State/province [14] 0 0
Michigan
Country [15] 0 0
United States of America
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Minnesota
Country [16] 0 0
United States of America
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Missouri
Country [17] 0 0
United States of America
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New Hampshire
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New Jersey
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United States of America
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New Mexico
Country [20] 0 0
United States of America
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New York
Country [21] 0 0
United States of America
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North Carolina
Country [22] 0 0
United States of America
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North Dakota
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United States of America
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Ohio
Country [24] 0 0
United States of America
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Pennsylvania
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United States of America
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South Carolina
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United States of America
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South Dakota
Country [27] 0 0
United States of America
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Tennessee
Country [28] 0 0
United States of America
State/province [28] 0 0
Texas
Country [29] 0 0
United States of America
State/province [29] 0 0
Utah
Country [30] 0 0
United States of America
State/province [30] 0 0
Washington
Country [31] 0 0
Argentina
State/province [31] 0 0
Buenos Aires
Country [32] 0 0
Argentina
State/province [32] 0 0
San Miguel de Tucuman
Country [33] 0 0
Austria
State/province [33] 0 0
Salzburg
Country [34] 0 0
Austria
State/province [34] 0 0
Wien
Country [35] 0 0
Bahamas
State/province [35] 0 0
Nassau
Country [36] 0 0
Belgium
State/province [36] 0 0
Bruxelles
Country [37] 0 0
Belgium
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Namur
Country [38] 0 0
Belgium
State/province [38] 0 0
Wilrijk
Country [39] 0 0
Bosnia and Herzegovina
State/province [39] 0 0
Banja Luka
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Bosnia and Herzegovina
State/province [40] 0 0
Sarajevo
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Brazil
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RJ
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Brazil
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RN
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Brazil
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RS
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Brazil
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SC
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Brazil
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SP
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Canada
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Alberta
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Canada
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Ontario
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Canada
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Quebec
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Colombia
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Bogota
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Colombia
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Bucaramanga
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Colombia
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Cali
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Colombia
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Pasto
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Czechia
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Brno
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Czechia
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Olomouc
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Czechia
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Praha 2
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Czechia
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Praha
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Denmark
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Vejle
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France
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Besancon
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France
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Clermont Ferrand
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France
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Lille
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Marseille
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France
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Montpellier
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Nancy
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France
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Paris
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France
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Poitiers
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France
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Saint Cloud
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France
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St Priest En Jarez
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Germany
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Essen
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Germany
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Halle
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Germany
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Hamburg
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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Magdeburg
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Germany
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Mainz
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Germany
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Minden
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Germany
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Muenchen
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Germany
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Trier
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Greece
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Athens
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Greece
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Heraklion
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Greece
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Larissa
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Guatemala
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Guatemala City
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Guatemala
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Guatemala
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Hungary
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Budapest
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Hungary
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Pécs
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Italy
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Calabria
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Italy
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Emilia-Romagna
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Italy
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Friuli-Venezia Giulia
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Italy
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Lombardia
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Italy
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Sicilia
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Italy
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Toscana
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Italy
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Umbria
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Japan
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Aichi
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Japan
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Ehime
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Japan
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Fukuoka
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Japan
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Gifu
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Japan
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Hiroshima
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Japan
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Hokkaido
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Japan
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Hyogo
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Japan
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Ishikawa
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Japan
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Iwate
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Japan
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Kagoshima
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Japan
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Kanagawa
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Japan
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Kumamoto
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Japan
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Kyoto
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Japan
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Miyagi
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Japan
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Niigata
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Japan
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Okayama
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Japan
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Osaka
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Japan
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Saitama
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Japan
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Shizuoka
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Japan
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Tokyo
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seoul
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Malaysia
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FED. Territory OF Kuala Lumpur
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Malaysia
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Selangor
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Mexico
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Guerrero
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Mexico
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Nuevo LEON
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Mexico
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Oaxaca
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Mexico
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Sonora
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Mexico
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Aguascalientes
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Mexico
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Toluca
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New Zealand
State/province [122] 0 0
Auckland
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New Zealand
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Hamilton
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North Macedonia
State/province [124] 0 0
Skopje
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Panama
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Panama
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Peru
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Arequipa
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Peru
State/province [127] 0 0
Lima
Country [128] 0 0
Peru
State/province [128] 0 0
Piura
Country [129] 0 0
Philippines
State/province [129] 0 0
Cebu City
Country [130] 0 0
Philippines
State/province [130] 0 0
San Juan
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Poland
State/province [131] 0 0
Bydgoszcz
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Poland
State/province [132] 0 0
Gdansk
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Poland
State/province [133] 0 0
Krakow
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Sutton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This randomized, 3-arm, multicenter, phase III study will evaluate the efficacy and safety of trastuzumab emtansine (T-DM1) with pertuzumab or trastuzumab emtansine (T-DM1) with pertuzumab-placebo (blinded for pertuzumab), versus the combination of trastuzumab (Herceptin) plus taxane (docetaxel or paclitaxel) in participants with HER2-positive progressive or recurrent locally advanced or previously untreated metastatic breast cancer. Participants will be randomized to 1 of 3 treatment arms (Arms A, B or C). Arm A will be open-label, whereas Arms B and C will be blinded.
Trial website
https://clinicaltrials.gov/study/NCT01120184
Trial related presentations / publications
Perez EA, de Haas SL, Eiermann W, Barrios CH, Toi M, Im YH, Conte PF, Martin M, Pienkowski T, Pivot XB, Burris HA 3rd, Stanzel S, Patre M, Ellis PA. Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine +/- pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer. BMC Cancer. 2019 May 30;19(1):517. doi: 10.1186/s12885-019-5687-0. Erratum In: BMC Cancer. 2019 Jun 24;19(1):620. doi: 10.1186/s12885-019-5831-x.
Bighin C, Pronzato P, Del Mastro L. Trastuzumab emtansine in the treatment of HER-2-positive metastatic breast cancer patients. Future Oncol. 2013 Jul;9(7):955-7. doi: 10.2217/fon.13.74.
Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01120184