Clinical Trials/NCT01120184

NCT01120184

Completed

Phase 3

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

Hoffmann-La Roche257 sites in 1 country1,095 target enrollmentJuly 31, 2010

ConditionsBreast Cancer

Interventionsdocetaxel paclitaxel trastuzumab [Herceptin]pertuzumab trastuzumab emtansine pertuzumab-placebo

Overview

Phase: Phase 3
Intervention: docetaxel
Conditions: Breast Cancer
Sponsor: Hoffmann-La Roche
Enrollment: 1095
Locations: 257
Primary Endpoint: Progression-Free Survival (PFS) According to IRF Assessment
Status: Completed
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 31, 2010

End Date

September 16, 2016

Last Updated

2 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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

Arms & Interventions

Trastuzumab + Taxane (docetaxel or paclitaxel)

Intervention: docetaxel

Trastuzumab + Taxane (docetaxel or paclitaxel)

Intervention: paclitaxel

Trastuzumab + Taxane (docetaxel or paclitaxel)

Intervention: trastuzumab [Herceptin]

Trastuzumab emtansine + pertuzumab

Intervention: pertuzumab

Trastuzumab emtansine + pertuzumab

Intervention: trastuzumab emtansine

Trastuzumab emtansine + pertuzumab placebo

Intervention: pertuzumab-placebo

Trastuzumab emtansine + pertuzumab placebo

Intervention: trastuzumab emtansine

Outcomes

Primary Outcomes

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)

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.

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)

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.

Secondary Outcomes

Percentage of Participants Who Died at 2 Years(From randomization until 2 years)
Percentage of Participants Experiencing Treatment Failure(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
Overall Survival (OS) at Clinical Cutoff(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(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))
One-Year Survival Rate(From randomization until 1 year)
Overall Survival Truncated at 2 Years(From randomization until 2 years)
PFS According to Investigator Assessment(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))
Time to Treatment Failure (TTF)(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
Percentage of Participants With Grade 5 Adverse Events(Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose))
Hospitalization Days(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
Percentage of Participants Who Died Prior to Clinical Cutoff(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 Grade ≥3 Adverse Events(Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose)
Percentage of Participants With Grade 3-4 Laboratory Parameters(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)
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(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 Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status(Baseline, Day 1 of every Cycle up to Clinical Data Cut (up to 48 months))
Percentage of Participants With Objective Response According to IRF Assessment(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 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(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 Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module(At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2)
Percentage of Participants With Hospitalization(Up to 48 months from randomization until clinical cutoff of 16-Sept-2014)
Percentage of Participants With Objective Response According to Investigator Assessment(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 Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module(At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2)
Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score(Baseline, Cycle 7 (Week 18))
Duration of Response According to IRF Assessment(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, PR, or Stable Disease (SD) According to IRF Assessment(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(Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014)
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels(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))
Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score(Baseline, Cycle 7 (Week 18))
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(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))
PFS According to IRF Assessment Among Those With High HER2 mRNA Levels(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 Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels(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 Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score(Baseline, Cycle 7 (Week 18))
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels(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 Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels(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))
OS at Clinical Cutoff Among Those With High HER2 mRNA Levels(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))
OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels(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 IRF Assessment Among Those With High HER2 mRNA Levels(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 IRF Assessment Among Those With Low HER2 mRNA Levels(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))