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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 March 2024
• Main ID: NCT01120184
• Date of registration: 28/04/2010
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• 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
• Date of first enrolment: July 31, 2010
• Target sample size: 1095
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT01120184
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Bahamas, Belgium, Bosnia and Herzegovina, Brazil, Canada, Colombia, Czech Republic, Czechia, Denmark, France, Germany, Greece, Guatemala, Hungary, Italy, Japan, Korea, Republic of, Macedonia, The Former Yugoslav Republic of, Malaysia, Mexico, New Zealand, North Macedonia, Panama, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Breast Cancer

Intervention(s)

Drug: docetaxel

Drug: pertuzumab-placebo

Drug: trastuzumab [Herceptin]

Drug: pertuzumab

Drug: paclitaxel

Drug: trastuzumab emtansine

Primary Outcome(s)

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)]

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 Outcome(s)

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

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)]

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)]

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)]

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)]

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

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

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)]

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)]

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)]

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]

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

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)]

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)]

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

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)]

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

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)]

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)]

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)]

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]

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]

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]

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)]

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)]

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]

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)]

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)]

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)]

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)]

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)]

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)]

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

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

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

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

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)]

Secondary ID(s)

BO22589

2009-017905-13

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.

Results

• Results available: Yes
• Date Posted: 23/02/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01120184