Metastatic Breast CancerPhase 2NCT00679211
A Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
A Phase 2 study testing Trastuzumab emtansine [Kadcyla] in people with Metastatic Breast Cancer, run by Genentech, Inc..
Trial summary
Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Trastuzumab emtansine [Kadcyla]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- No sites listed yet
- Study dates
- Aug 2008to Apr 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed study-specific Informed Consent Form(s)
- Age ≥ 18 years
- Histologically documented breast cancer
- HER2-positive disease
- Metastatic breast cancer
- Disease progression on the last chemotherapy regimen received in the metastatic setting
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- Prior treatment with an anthracycline, trastuzumab, a taxane, lapatinib, and capecitabine in the neoadjuvant, adjuvant, locally advanced, or metastatic setting and prior treatment with at least two lines of therapy (a line of therapy can be a combination of two agents or single-agent chemotherapy) in the metastatic setting
- At least two lines of anti-HER2 therapy must have been given in the metastatic setting as monotherapy or combined with chemotherapy or hormonal therapy. The HER2-targeted agent can include trastuzumab, lapatinib, or an investigational agent with HER2-inhibitory activity.
- A minimum of 6 weeks of trastuzumab for the treatment of metastatic disease is required
- Patients must have had at least 14 days of exposure in the metastatic setting to lapatinib and capecitabine (given together or separately) unless they were intolerant of lapatinib and/or capecitabine
Who cannot join
- Chemotherapy ≤ 21 days before enrollment
- Trastuzumab ≤ 21 days before enrollment
- Hormone therapy ≤ 7 days before enrollment
- Granulocyte-stimulating agent < 14 days before enrollment
- Investigational therapy ≤ 28 days before enrollment
- Previous radiotherapy for treatment of metastatic breast cancer ≤ 21 days before enrollment
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- 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 3 months of the first study treatment
- History of intolerance (including Grade 3-4 infusion reaction) or hypersensitivity to trastuzumab or murine proteins
- History of exposure to the following cumulative doses of anthracyclines: Doxorubicin or liposomal doxorubicin > 500 mg/m^2; Epirubicin > 900 mg/m^2; Mitoxantrone > 120 mg/m^2 and idarubicin > 90 mg/m^2
- Peripheral neuropathy of Grade ≥ 3 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0
- History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or basal cell carcinoma
- Current unstable angina
- History of symptomatic congestive heart failure (CHF), or ventricular arrhythmia requiring treatment
- History of myocardial infarction within 6 months of enrollment
- Left ventricular ejection fraction (LVEF) < 50% within 28 days of enrollment
- History of decreased LVEF to < 50% or symptomatic CHF with previous adjuvant trastuzumab treatment
- Severe dyspnea at rest due to complications of advanced malignancy or requiring current continuous oxygen therapy
- Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease)
- Major surgical procedure or significant traumatic injury within 28 days before enrollment or anticipation of the need for major surgery during the course of study treatment
- Current pregnancy or lactation
- Current known infection with human immunodeficiency virus (HIV), active hepatitis B, and/or hepatitis C virus
- Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol
About this study
Official title: A Phase II, Single-Arm, Open-Label Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Trastuzumab emtansine [Kadcyla]
- Keywords
- HER2-positive breast cancer, HER2, MBC, Trastuzumab emtansine
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab emtansine [Kadcyla]Drug
Also called Trastuzumab-MCC-DM1, T-DM1
Intravenous repeating dose
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab emtansine | Experimental | Trastuzumab emtansine (T-DM1) was administered to participants at a dose of 3.6 mg/kg by intravenous (IV) infusion every 3 weeks until documented disease progression, unmanageable toxicity, or study termination. Receives: Drug: Trastuzumab emtansine [Kadcyla] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review
Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive occasions ≥ 4 weeks apart, assessed using Response Evaluation Criteria in Solid Tumors (RECIST).
CR: the disappearance of all target lesions and all nontarget lesions and normalization of tumor marker level and no new lesions.
PR: disappearance of all target lesions and persistence of ≥ 1 nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing nontarget lesions.
The primary data cut-off date was 17 September 2009 (approximately 6 months after the last patient was enrolled). The final efficacy analysis was performed using a data cut-off date of 1 January 2010 (approximately 9 months after the last patient was enrolled).
Measured: From randomization until the primary analysis data cut-off date of September 2009 (6 months after last patient enrolled) and until the final efficacy analysis cut-off date of 1 January 2010 (approximately 9 months after the last patient enrolled).
Secondary outcomes (7)
Duration of Objective Response as Assessed Through Independent Radiologic Review
For participants who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a participant's objective response to the time of disease progression or death on study (i.e., death from any cause within 30 days of the last dose of study drug), whichever occurred first. Response was assessed by the independent review facility.
Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Progression-free Survival as Assessed Through Independent Radiologic Review
Progression-Free Survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (i.e., death from any cause within 30 days of the last dose of study drug), whichever occurred first.
Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. Disease progression was assessed by the independent review facility.
For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Percentage of Participants With Clinical Benefit Based on Independent Radiologic Review
Clinical benefit was defined as participants who achieved an objective response (confirmed complete or partial response) between randomization and 1 January 2010, or with stable disease at 6 months. Stable disease at 6 months was defined as participants who achieved at least stable disease based on tumor assessments by the independent review facility, and remained alive and progression-free at 6 months.
Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started, and no new lesions and/or unequivocal progression of existing nontarget lesions. Response was assessed by the independent review facility.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Objective Response Based on Investigator Assessment
Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive occasions ≥ 4 weeks apart, assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Response was assessed by the study Investigator.
CR: the disappearance of all target lesions and all nontarget lesions and normalization of tumor marker level and no new lesions.
PR: disappearance of all target lesions and persistence of ≥ 1 nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing nontarget lesions.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Progression-free Survival Based on Investigator Assessment
Progression-Free Survival (PFS) was defined as the time from the first day of study treatment to documented disease progression or death on study (i.e., death from any cause within 30 days of the last dose of study drug), whichever occurred first.
Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
For patients who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate PFS.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Duration of Objective Response Based on Investigator Assessment
For participants who achieved an objective response, duration of objective response was defined as the time from the first tumor assessment that supported a participant's objective response to the time of disease progression or death on study (i.e., death from any cause within 30 days of the last dose of study drug), whichever occurred first. Response was determined by the Investigator's assessment.
Disease progression was at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions.
For participants who experienced no disease progression and did not die while on study, data were censored at the date of the last tumor assessment. Kaplan-Meier methodology was used to estimate the duration of objective response.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Percentage of Participants With Clinical Benefit Based on Investigator Assessment
Clinical benefit was defined as participants with an objective response (confirmed complete or partial response) or stable disease at 6 months. Patients with stable disease at 6 months were defined as patients who achieved at least stable disease based on tumor assessments and remained alive and progression free at 6 months. Response was based on the Investigator's assessment.
Measured: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2008 (estimated)
- Study startAug 2008
- Primary completionSep 2009
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Genentech, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genentech, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ellie Guardino, M.D., PhD., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00679211
- Sponsor's protocol ID
- TDM4374g
- Status last verified
- May 2013
- First submitted
- 14 May 2008
- Last updated
- 31 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single-Arm, Open-Label Study of Trastuzumab-Mcc-DM1 Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00679211
- Acronym / sponsor ID
- TDM4374g
- Conditions
- Metastatic Breast Cancer
- Keywords
- HER2-positive breast cancer, HER2, MBC, Trastuzumab emtansine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Genentech, Inc.Industry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Sep 2009 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 16 May 2008 (estimated)
- Results
- Posted 23 Apr 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study of trastuzumab emtansine (T-DM1) administered to patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab emtansine | Experimental | Drug: Trastuzumab emtansine [Kadcyla]Trastuzumab emtansine (T-DM1) was administered to participants at a dose of 3.6 mg/kg by intravenous (IV) infusion every 3 weeks until documented disease progression, unmanageable toxicity, or study termination. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed study-specific Informed Consent Form(s)
- Age ≥ 18 years
- Histologically documented breast cancer
- HER2-positive disease
- Metastatic breast cancer
Key exclusion criteria (22 listed)
- Chemotherapy ≤ 21 days before enrollment
- Trastuzumab ≤ 21 days before enrollment
- Hormone therapy ≤ 7 days before enrollment
- Granulocyte-stimulating agent < 14 days before enrollment
- Investigational therapy ≤ 28 days before enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Trastuzumab emtansine [Kadcyla]Also: Trastuzumab-MCC-DM1, T-DM1Intravenous repeating dose | Drug | Trastuzumab emtansine |
Primary outcome
Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review
Time frame: From randomization until the primary analysis data cut-off date of September 2009 (6 months after last patient enrolled) and until the final efficacy analysis cut-off date of 1 January 2010 (approximately 9 months after the last patient enrolled).
Objective response was defined as a complete response (CR) or partial response (PR) determined on two consecutive occasions ≥ 4 weeks apart, assessed using Response Evaluation Criteria in Solid Tumors (RECIST). CR: the disappearance of all target lesions and all nontarget lesions and normalization of tumor marker level and no new lesions. PR: disappearance of all target lesions and persistence of ≥ 1 nontarget lesion(s) and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing nontarget lesions. The primary data cut-off date was 17 September 2009 (approximately 6 months after the last patient was enrolled). The final efficacy analysis was performed using a data cut-off date of 1 January 2010 (approximately 9 months after the last patient was enrolled).
7 secondary outcomes
Duration of Objective Response as Assessed Through Independent Radiologic Review
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Progression-free Survival as Assessed Through Independent Radiologic Review
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Percentage of Participants With Clinical Benefit Based on Independent Radiologic Review
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Objective Response Based on Investigator Assessment
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Progression-free Survival Based on Investigator Assessment
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Duration of Objective Response Based on Investigator Assessment
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Percentage of Participants With Clinical Benefit Based on Investigator Assessment
Time frame: From randomization until 1 January 2010, approximately 9 months after the last participant was enrolled.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ellie Guardino, M.D., PhD. study director
Genentech, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab emtansine [Kadcyla] in people with Metastatic Breast Cancer, run by Genentech, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Apr 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With an Objective Response as Assessed Through Independent Radiologic Review (time frame: From randomization until the primary analysis data cut-off date of September 2009 (6 months after last patient enrolled) and until the final efficacy analysis cut-off date of 1 January 2010 (approximately 9 months after the last patient enrolled).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2017.