A Study of the Efficacy and Safety of Trastuzumab Emtansine (Trastuzumab-MCC-DM1) vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease
A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metastatic Disease
2 other identifiers
interventional
137
0 countries
N/A
Brief Summary
This was a Phase II, randomized, multicenter, international, 2-arm, open-label clinical trial designed to explore the efficacy and safety of trastuzumab emtansine (T-DM1) relative to the combination of trastuzumab and docetaxel in patients with human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced breast cancer and/or metastatic breast cancer who have not received prior chemotherapy for metastatic disease.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 breast-cancer
Started Sep 2008
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 14, 2008
CompletedFirst Posted
Study publicly available on registry
May 16, 2008
CompletedStudy Start
First participant enrolled
September 1, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 1, 2010
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2012
CompletedResults Posted
Study results publicly available
May 20, 2013
CompletedJanuary 9, 2014
December 1, 2013
2.2 years
May 14, 2008
February 22, 2013
December 9, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)
PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day.
Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
Secondary Outcomes (7)
Overall Survival
Baseline through the data cut-off date of 31 Aug 2011 (up to 2 years, 11 months)
Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
Time to Symptom Progression
Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
- +2 more secondary outcomes
Study Arms (2)
Trastuzumab emtansine
EXPERIMENTALPatients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) administered over 30-90 minutes every 3 weeks on Day 1 of each 21-day cycle.
Trastuzumab + docetaxel
ACTIVE COMPARATORPatients received a loading dose of trastuzumab 8 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of Cycle 1 followed by trastuzumab 6 mg/kg IV + docetaxel 75 or 100 mg/m\^2 IV on Day 1 of all subsequent 21-day cycles.
Interventions
The total dose depended on the patient's weight on Day 1 of each cycle. Trastuzumab emtansine was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease (or until second disease progression for patients who crossed over), unacceptable toxicity, or study closure, whichever occurred first.
The dose of trastuzumab was recalculated if body weight changed by more than ±10% from baseline. Trastuzumab was administered every 3 weeks until investigator-assessed radiographic or clinical progressive disease, or unmanageable toxicity. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.
Docetaxel was given at a dose of 75 or 100 mg/m\^2 based on the investigator's decision. Patients in the trastuzumab + docetaxel arm who discontinued study treatment because of progressive disease were eligible to cross-over to trastuzumab emtansine treatment until a second progressive disease event, clinical deterioration, and/or intolerance.
Eligibility Criteria
You may qualify if:
- Histologically or cytologically confirmed adenocarcinoma of the breast with locally advanced or metastatic disease, and a candidate for chemotherapy.
- Human epidermal growth factor receptor 2 (HER2)-positive.
- No prior chemotherapy for their metastatic breast cancer (MBC).
- Measurable disease.
- Age ≥ 18 years.
- For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or 2 effective forms of non-hormonal contraception by the patient and/or partner. Contraception use must continue for the duration of study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study.
You may not qualify if:
- History of any chemotherapy for MBC.
- An interval of \< 6 months from the completion of cytotoxic chemotherapy in the neo-adjuvant or adjuvant setting until the time of metastatic diagnosis.
- Trastuzumab ≤ 21 days prior to randomization.
- Hormone therapy \< 7 days prior to randomization.
- Current peripheral neuropathy of Grade ≥ 3.
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with a similar outcome as those previously mentioned.
- Previous radiotherapy for the treatment of unresectable, locally advanced or metastatic breast cancer is not allowed if more than 25% of marrow-bearing bone has been irradiated or the last fraction of radiotherapy has been administered within approximately 3 weeks prior to randomization.
- Brain metastases that are untreated, symptomatic, or require therapy to control symptoms or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to randomization.
- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin \> 500 mg/m\^2; epirubicin \> 900 mg/m\^2; mitoxantrone \> 120mg/m\^2 and idarubicin \> 90 mg/m\^2.
- Current unstable angina.
- History of symptomatic congestive heart failure, or ventricular arrhythmia requiring treatment.
- History of myocardial infarction within 6 months prior to randomization.
- Left ventricular ejection fraction (LVEF) below 50% within approximately 28 days prior to randomization.
- History of decreased LVEF or symptomatic congestive heart failure (CHF) with previous adjuvant trastuzumab treatment.
- Cardiac troponin I ≥ 0.2 ng/mL within 28 days of randomization.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (2)
Perez EA, Hurvitz SA, Amler LC, Mundt KE, Ng V, Guardino E, Gianni L. Relationship between HER2 expression and efficacy with first-line trastuzumab emtansine compared with trastuzumab plus docetaxel in TDM4450g: a randomized phase II study of patients with previously untreated HER2-positive metastatic breast cancer. Breast Cancer Res. 2014 May 23;16(3):R50. doi: 10.1186/bcr3661.
PMID: 24887458DERIVEDHurvitz SA, Dirix L, Kocsis J, Bianchi GV, Lu J, Vinholes J, Guardino E, Song C, Tong B, Ng V, Chu YW, Perez EA. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol. 2013 Mar 20;31(9):1157-63. doi: 10.1200/JCO.2012.44.9694. Epub 2013 Feb 4.
PMID: 23382472DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Communications
- Organization
- Genentech, Inc.
Study Officials
- STUDY DIRECTOR
Ellie Guardino, MD/PhD
Genentech, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 14, 2008
First Posted
May 16, 2008
Study Start
September 1, 2008
Primary Completion
November 1, 2010
Study Completion
May 1, 2012
Last Updated
January 9, 2014
Results First Posted
May 20, 2013
Record last verified: 2013-12