Metastatic Breast CancerPhase 1/2NCT00875979
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
A Phase 1/2 study testing Trastuzumab emtansine [Kadcyla] 3.0 mg/kg, Trastuzumab emtansine [Kadcyla] 3.6 mg/kg and Pertuzumab 420 mg in people with Metastatic Breast Cancer, run by Hoffmann-La Roche at 20 sites in 7 countries.
Trial summary
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… 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] 3.0 mg/kg, Trastuzumab emtansine [Kadcyla] 3.6 mg/kg and Pertuzumab 420 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 67 participants
- Where
- 20 sitesin 7 countries
- Study dates
- May 2009to Aug 2011
- Phase
- Phase 1/2
- 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
- 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.
Who cannot join
- 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.
Trial locations and contacts
20 sites in 7 countries.
20 sites in 7 countries
United States10 sites
Study site
Boca Raton, Florida, 33428
Study site
Chapel Hill, North Carolina, 27514
Study site
Deerfield Beach, Florida, 33442
Study site
Indianapolis, Indiana, 46202
Study site
Maywood, Illinois, 60153
Study site
Nashville, Tennessee, 37203
Study site
Philadelphia, Pennsylvania, 19104
Study site
Philadelphia, Pennsylvania, 19111
Study site
Rockville, Maryland, 20850-3348
Study site
Wichita, Kansas, 67214
Canada2 sites
Study site
Montreal, Quebec, H3A 1A1
Study site
Vancouver, British Columbia, V5Z 1H5
About this study
Official title: 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.
Read the 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.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Trastuzumab emtansine [Kadcyla] 3.0 mg/kg, Trastuzumab emtansine [Kadcyla] 3.6 mg/kg, Pertuzumab 420 mg
- Keywords
- MBC, Breast Cancer, HER2+, HER2+ breast cancer, HER2 positive breast cancer, herceptin, 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] 3.0 mg/kgDrug
Also called trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1
Trastuzumab emtansine was provided as a single-use lyophilized formulation.
Trastuzumab emtansine [Kadcyla] 3.6 mg/kgDrug
Also called trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1
Trastuzumab emtansine was provided as a single-use lyophilized formulation.
Pertuzumab 420 mgDrug
Also called Perjeta
Pertuzumab was provided as a single-use formulation.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg | Experimental | 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. Receives: Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg; Drug: Pertuzumab 420 mg |
| Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg | Experimental | 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. Receives: Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg; Drug: Pertuzumab 420 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Measured: Baseline through the end of the study (up to 2 years 3 months)
Secondary outcomes (2)
Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Measured: Baseline through the end of the study (up to 2 years 3 months)
Progression-free Survival Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
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.
Measured: Baseline through the end of the study (up to 2 years 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2009 (estimated)
- Study startMay 2009
- Primary completionAug 2011
- Study completionAug 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- Elaine K. Wong, M.Sc., M.D., Study director, Genentech, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00875979
- Sponsor's protocol ID
- BO22495
- Other IDs
- TDM4373g
- Status last verified
- Dec 2013
- First submitted
- 2 Apr 2009
- Last updated
- 24 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Miller KD, Dieras V, Harbeck N, Andre F, Mahtani RL, Gianni L, Albain KS, Crivellari D, Fang L, Michelson G, de Haas SL, Burris HA. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014 May 10;32(14):1437-44. doi: 10.1200/JCO.2013.52.6590. Epub 2014 Apr 14.
PubMed 24733796
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00875979
- Acronym / sponsor ID
- BO22495
- Conditions
- Metastatic Breast Cancer
- Keywords
- MBC, Breast Cancer, HER2+, HER2+ breast cancer, HER2 positive breast cancer, herceptin, Trastuzumab emtansine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Collaborators
- Roche Pharma AG
- Study start
- May 2009
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 6 Apr 2009 (estimated)
- Results
- Posted 18 Jul 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg | Experimental | Drug: Trastuzumab emtansine [Kadcyla] 3.0 mg/kg, Drug: Pertuzumab 420 mgPatients 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. |
| Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg | Experimental | Drug: Trastuzumab emtansine [Kadcyla] 3.6 mg/kg, Drug: Pertuzumab 420 mgPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
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] 3.0 mg/kgAlso: trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1Trastuzumab emtansine was provided as a single-use lyophilized formulation. | Drug | Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg |
| Trastuzumab emtansine [Kadcyla] 3.6 mg/kgAlso: trastuzumab-DM1, trastuzumab-MCC-DM1, T-DM1Trastuzumab emtansine was provided as a single-use lyophilized formulation. | Drug | Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg |
| Pertuzumab 420 mgAlso: PerjetaPertuzumab was provided as a single-use formulation. | Drug | Trastuzumab emtansine 3.0 mg/kg + pertuzumab 420 mg, Trastuzumab emtansine 3.6 mg/kg + pertuzumab 420 mg |
Primary outcome
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)
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.
2 secondary outcomes
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24733796Miller KD, Dieras V, Harbeck N, Andre F, Mahtani RL, Gianni L, Albain KS, Crivellari D, Fang L, Michelson G, de Haas SL, Burris HA. Phase IIa trial of trastuzumab emtansine with pertuzumab for patients with human epidermal growth factor receptor 2-positive, locally advanced, or metastatic breast cancer. J Clin Oncol. 2014 May 10;32(14):1437-44. doi: 10.1200/JCO.2013.52.6590. Epub 2014 Apr 14.
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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.
Elaine K. Wong, M.Sc., M.D. study director
Genentech, Inc.
20 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Trastuzumab emtansine [Kadcyla] 3.0 mg/kg, Trastuzumab emtansine [Kadcyla] 3.6 mg/kg and Pertuzumab 420 mg in people with Metastatic Breast Cancer, run by Hoffmann-La Roche at 20 sites in 7 countries.
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 7 inclusion and 7 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 24 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, France, Italy, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 18 Jul 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?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00875979, which also lists 1 linked publication.
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 24 Dec 2013.