- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00875979
A Study of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
December 20, 2013 updated by: Hoffmann-La Roche
A Phase Ib/II, Open-label Study of the Safety, Tolerability, and Efficacy of Trastuzumab Emtansine (Trastuzumab-MCC-DM1, T-DM1) in Combination With Pertuzumab Administered Intravenously to Patients With Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Locally Advanced or Metastatic Breast Cancer Who Have Previously Received Trastuzumab
This was a multi-institutional, multinational, open-label, single-arm Phase Ib/II study designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of trastuzumab emtansine (trastuzumab-MCC-DM1) administered by intravenous (IV) infusion in combination with pertuzumab in patients with human epidermal growth factor receptor-2 (HER2)-positive locally advanced or metastatic breast cancer who had previously received trastuzumab.
Study Overview
Status
Completed
Conditions
Detailed Description
There were 2 phases in the study, a Dose Escalation phase (Phase 1b) and a Dose Expansion phase (Phase 2a).
In the Dose Escalation phase, 3 patients were enrolled at the first dose level (3.0 mg/kg trastuzumab emtansine) and and 6 patients were enrolled at the second dose level (3.6 mg/kg trastuzumab emtansine).
An additional 58 patients were enrolled at the 3.6 mg/kg trastuzumab emtansine dose level in the Dose Expansion phase (Phase 2a) of the study.
Study Type
Interventional
Enrollment (Actual)
67
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Bruxelles, Belgium, 1000
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 1H5
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Quebec
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Montreal, Quebec, Canada, H3A 1A1
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Paris, France, 75248
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Villejuif, France, 94805
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Köln, Germany, 50924
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Aviano, Italy, 33081
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Milano, Italy, 20133
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Barcelona, Spain, 08035
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Valencia, Spain, 46010
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Florida
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Boca Raton, Florida, United States, 33428
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Deerfield Beach, Florida, United States, 33442
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Illinois
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Maywood, Illinois, United States, 60153
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Indiana
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Indianapolis, Indiana, United States, 46202
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Kansas
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Wichita, Kansas, United States, 67214
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Maryland
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Rockville, Maryland, United States, 20850-3348
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
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Philadelphia, Pennsylvania, United States, 19111
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Tennessee
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Nashville, Tennessee, United States, 37203
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Histologically documented human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer.
- Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments.
- Prior trastuzumab in any line of therapy.
- No prior trastuzumab emtansine (T-DM1) or pertuzumab therapy.
- Measurable disease.
- For women of childbearing potential, agreement to use an effective form of contraception and to continue its use for the duration of the study.
- Life expectancy ≥ 90 days.
Exclusion Criteria:
- Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal, or radiotherapy for the treatment of breast cancer, with the following exceptions: Hormone-replacement therapy or oral contraceptives; palliative radiation therapy involving ≤ 25% of marrow-bearing bone if administered ≥ 14 days prior to first study treatment.
- History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued.
- Peripheral neuropathy of Grade ≥ 2.
- History of clinically significant cardiac dysfunction.
- Current severe, uncontrolled systemic disease, eg, clinically significant cardiovascular, pulmonary, or metabolic disease.
- Brain metastases that are untreated, progressive, or have required any type of therapy to control symptoms from brain metastases within 60 days of the first study treatment.
- History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg
Patients received trastuzumab emtansine 3.0 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation.
Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
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Trastuzumab emtansine was provided as a single-use lyophilized formulation.
Other Names:
Pertuzumab was provided as a single-use formulation.
Other Names:
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Experimental: Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg
Patients received trastuzumab emtansine 3.6 mg/kg intravenously (IV) on Day 1 of every 3 week cycle until progressive disease, intolerable toxicity, initiation of another anti-cancer therapy, or patient discontinuation.
Patients also received a loading dose of 840 mg of pertuzumab IV on Day 1 of Cycle 1 followed by pertuzumab 420 mg IV on Day 1 of every subsequent 3 week cycle.
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Pertuzumab was provided as a single-use formulation.
Other Names:
Trastuzumab emtansine was provided as a single-use lyophilized formulation.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Baseline through the end of the study (up to 2 years 3 months)
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A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart.
For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.
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Baseline through the end of the study (up to 2 years 3 months)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Baseline through the end of the study (up to 2 years 3 months)
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Duration of objective response was defined as the time from initial response to disease progression (PD) or death from any cause.
For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions.
For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically.
All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
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Baseline through the end of the study (up to 2 years 3 months)
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Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame: Baseline through the end of the study (up to 2 years 3 months)
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Progression-free survival was defined as the time from randomization to first documented disease progression (PD) or death due to any cause within 30 days of the last treatment, whichever occurred first.
For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions.
For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions.
Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically.
All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions.
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Baseline through the end of the study (up to 2 years 3 months)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Director: Elaine K. Wong, M.Sc., M.D., Genentech, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
May 1, 2009
Primary Completion (Actual)
August 1, 2011
Study Completion (Actual)
August 1, 2011
Study Registration Dates
First Submitted
April 2, 2009
First Submitted That Met QC Criteria
April 2, 2009
First Posted (Estimate)
April 6, 2009
Study Record Updates
Last Update Posted (Estimate)
December 24, 2013
Last Update Submitted That Met QC Criteria
December 20, 2013
Last Verified
December 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Trastuzumab
- Maytansine
- Ado-Trastuzumab Emtansine
- Pertuzumab
Other Study ID Numbers
- BO22495
- TDM4373g (Other Identifier: Genentech)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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