TriangleNCT01120184 · CITED IN SOURCE DOCUMENTS
A Study of Trastuzumab Emtansine (T-DM1) Plus Pertuzumab/Pertuzumab Placebo Versus Trastuzumab [Herceptin] Plus a Taxane in Participants With Metastatic Breast Cancer (MARIANNE)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2024-03-04
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.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment
Progression-Free Survival (PFS) According to IRF Assessment
Percentage of Participants Who Died Prior to Clinical Cutoff
Overall Survival (OS) at Clinical Cutoff
Percentage of Participants With Death or Disease Progression According to Investigator Assessment
PFS According to Investigator Assessment
Percentage of Participants Experiencing Treatment Failure
Time to Treatment Failure (TTF)
One-Year Survival Rate
Percentage of Participants With Grade ≥3 Adverse Events
Percentage of Participants Who Died at 2 Years
Overall Survival Truncated at 2 Years
Percentage of Participants With Grade 5 Adverse Events
Percentage of Participants With Grade 3-4 Laboratory Parameters
Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status
Hospitalization Days
Percentage of Participants With Hospitalization
Percentage of Participants With Objective Response According to IRF Assessment
Percentage of Participants With Objective Response According to Investigator Assessment
Duration of Response According to IRF Assessment
Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD) According to IRF Assessment
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
Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module
Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module
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 to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score
Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score
Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
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
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels
PFS According to IRF Assessment Among Those With High HER2 mRNA Levels
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels
PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels
OS at Clinical Cutoff Among Those With High HER2 mRNA Levels
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels
OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- intervention Names
- Drug: docetaxel
- Drug: paclitaxel
- Drug: trastuzumab [Herceptin]
- label
- Trastuzumab + Taxane (docetaxel or paclitaxel)
- type
- EXPERIMENTAL
- intervention Names
- Drug: pertuzumab
- Drug: trastuzumab emtansine
- label
- Trastuzumab emtansine + pertuzumab
- type
- EXPERIMENTAL
- intervention Names
- Drug: pertuzumab-placebo
- Drug: trastuzumab emtansine
- label
- Trastuzumab emtansine + pertuzumab placebo
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Trastuzumab + Taxane (docetaxel or paclitaxel)
- description
- 75 mg/m2 or 100 mg/m2 intravenously every 3 weeks for a minimum of 6 cycles.
- name
- docetaxel
- type
- DRUG
- arm Group Labels
- Trastuzumab + Taxane (docetaxel or paclitaxel)
- description
- 80 mg/m2 intravenously weekly for a minimum of 18 weeks
- name
- paclitaxel
- type
- DRUG
- arm Group Labels
- Trastuzumab emtansine + pertuzumab
- description
- 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
- name
- pertuzumab
- type
- DRUG
- arm Group Labels
- Trastuzumab emtansine + pertuzumab placebo
- description
- 840 mg intravenously on day 1 of cycle 1 followed by 420 mg intravenously every 3 weeks in subsequent cycles
- name
- pertuzumab-placebo
- type
- DRUG
- arm Group Labels
- Trastuzumab + Taxane (docetaxel or paclitaxel)
- description
- 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.
- name
- trastuzumab [Herceptin]
- type
- DRUG
- arm Group Labels
- Trastuzumab emtansine + pertuzumab
- Trastuzumab emtansine + pertuzumab placebo
- description
- 3.6 mg/kg intravenously every 3 weeks
- name
- trastuzumab emtansine
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- who Masked
- PARTICIPANT
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1095
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- Tumor assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and 5-millimeter (mm) increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.
- measure
- 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)
- description
- Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding confidence intervals (CIs) were computed using the Brookmeyer-Crowley method.
- measure
- 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)
- secondary Outcomes
- description
- The percentage of participants who died prior to clinical cutoff was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.
- measure
- 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)
- description
- OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
- measure
- 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)
- description
- Tumor assessments were performed by the investigator according to RECIST version 1.1. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.
- measure
- 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)
- description
- Tumor assessments were performed by the investigator according to RECIST version 1.1. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
- measure
- 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)
- description
- Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. The percentage of participants with treatment failure was calculated as \[number of participants with event divided by the number analyzed\] multiplied by 100.
- measure
- Percentage of Participants Experiencing Treatment Failure
- time Frame
- Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
- description
- Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method.
- measure
- Time to Treatment Failure (TTF)
- time Frame
- Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
- description
- The percentage of participants alive at 1 year after randomization was estimated as the one-year survival rate using Kaplan-Meier analysis, and corresponding CIs were computed using Greenwood's estimate of the standard error.
- measure
- One-Year Survival Rate
- time Frame
- From randomization until 1 year
- description
- Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. Grade 5: Death.
- measure
- 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
- measure
- Percentage of Participants Who Died at 2 Years
- time Frame
- From randomization until 2 years
- description
- Overall Survival truncated at 2 years was defined as the percentage of participants alive at 2 years.
- measure
- Overall Survival Truncated at 2 Years
- time Frame
- From randomization until 2 years
- description
- Adverse events were graded according to NCI CTCAE version 4.0. Grade 5 adverse events are those events which led to death.
- measure
- 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)
- description
- Laboratory results were graded according to NCI CTCAE version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival.
- measure
- 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
Full study description
- 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.
Source references
- references
- citation
- 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.
- pmid
- 31146717
- type
- DERIVED
- citation
- 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.
- pmid
- 23837759
- type
- DERIVED
- citation
- Scott AM, Wolchok JD, Old LJ. Antibody therapy of cancer. Nat Rev Cancer. 2012 Mar 22;12(4):278-87. doi: 10.1038/nrc3236.
- pmid
- 22437872
- type
- DERIVED
Source notices and limitations
Discovery and provenance
- release id
- ctgov-registry-7ad944f6deaf1f5cd6122126
- edge id
- nct-edge-cecd7faf8d6b93d11b76
- requested nct id
- NCT01120184
- primary nct id
- NCT01120184
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- payload sha256
- 0f4b53a74464d1a628d7480802c69ffcf254069459dca8c45dbb013019e96b7c
- payload
- clinical indication matching status
- not_inferred
- end exclusive
- true
- id
- nct-edge-cecd7faf8d6b93d11b76
- link basis
- explicit_NCT_identifier_in_acquired_source
- nct id
- NCT01120184
- occurrences
- context exact
- /div></li><li> The role of T-DM1 as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III <a href="/clinicaltrials/NCT01120184">MARIANNE</a> trial (NCT01120184).[<a href="#cit/section_10.78">78</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810025&version=HealthProfessional&
- end
- 634255
- exact text
- NCT01120184
- start
- 634244
- context exact
- as first-line treatment of metastatic HER2-overexpressed breast cancer was evaluated in the phase III <a href="/clinicaltrials/NCT01120184">MARIANNE</a> trial (NCT01120184).[<a href="#cit/section_10.78">78</a>][<a href="/Common/PopUps/popDefinition.aspx?id=810025&version=HealthProfessional&language=English" onclick="javas
- end
- 634288
- exact text
- NCT01120184
- start
- 634277
- offset unit
- unicode_code_points
- source file
- /tmp/cancer-full-research/nci/raw/29bf1e5a1d739974ed.html
- source file sha256
- 862f78faa9e4cbedc19f9ffcaeba97e029ba51b72bb3b81fc67aa8b6adf96904
- source json pointer
- Source null
- source kind
- nci_explicit_reference_or_link
- source record id
- Source null
- source retrieved at
- 2026-09-09T23:21:35.419733+00:00
- source string basis
- UTF-8_text_with_universal_newline_translation
- source string sha256
- 536430925e3b0008edd3fb69a869d5645bd6b6dc5c84c21ddf1b3e24f089874c
- source title
- Breast Cancer Treatment (PDQ®)–Health Professional Version
- source update dates
- context
- Updated: April 25, 2025
- datetime
- 2025-04-25T12:00:00Z
- display
- April 25, 2025
Preserved source evidence · Not medical advice