Breast CancerPhase 2NCT01196052
A Study of Trastuzumab Emtansine (T-DM1) Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage Herceptin (HER)2-positive Breast Cancer
A Phase 2 study testing Trastuzumab emtansine in people with Breast Cancer, run by Hoffmann-La Roche at 44 sites in 8 countries.
Trial summary
This single-arm open-label study assessed the safety, feasibility, and efficacy of trastuzumab emtansine (T-DM1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Trastuzumab emtansine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 153 participants
- Where
- 44 sitesin 8 countries
- Study dates
- Oct 2010to Jun 2013
- 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
- Adult patients ≥ 18 years of age.
- Locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive breast cancer documented at a local laboratory (patients with inflammatory breast cancer must be able to have a core needle biopsy).
- Herceptin (HER)2-positive tumor, confirmed by central testing using immunohistochemistry (IHC) and in situ hybridization (ISH) methods.
- Willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (AC) OR 5-fluorouracil (FU)/epirubicin/ cyclophosphamide (FEC) in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment.
- 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 should use condoms for the duration of the study. Specific country requirements will be followed.
- Negative results of serum pregnancy test for premenopausal women of reproductive capacity and for women < 12 months after menopause.
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- Patients may enroll before or after AC/FEC chemotherapy has completed.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate hematologic, biochemistry, and cardiac assessments.
Who cannot join
- Stage IV breast cancer or bilateral breast cancer.
- Pregnant or breastfeeding women.
- History of other malignancy within the previous 5 years, except contralateral breast cancer and ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS), appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with outcome similar to those mentioned above.
- Radiation therapy, immunotherapy, or biotherapy within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study enrollment is allowed. Patients receiving AC/FEC in a similar fashion to the study treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be allowed to enroll in the study after the completion of their AC/FEC. No other prior history of cardiotoxic chemotherapy is allowed.
- Active cardiac history.
- Current chronic daily treatment with oral corticosteroids or equivalent.
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- Patients with severe dyspnea at rest or requiring supplementary oxygen therapy.
- Active, unresolved infections at screening.
- Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.
- Major surgery within 4 weeks before enrollment that is unrelated to the breast cancer.
- Patients for whom concomitant radiotherapy + T-DM1 may be contraindicated yet radiation therapy is planned.
- Known hypersensitivity to any of the study drugs or derivatives, including murine proteins.
- Grade ≥ 2 peripheral neuropathy at Baseline.
Trial locations and contacts
44 sites in 8 countries.
44 sites in 8 countries
United States15 sites
Study site
Boston, Massachusetts, 02115
Study site
Boston, Massachusetts, 02130
Study site
Durham, North Carolina, 27710
Study site
Fort Myers, Florida, 33916
Study site
Kensignton, Maryland, 20895
Study site
Lafayette, Indiana, 47905
Study site
Lake Success, New York, 11042
Study site
Nashville, Tennessee, 37203
Study site
Omaha, Nebraska, 68114
Study site
San Antonio, Texas, 78258
Study site
Scarborough, Maine, 04074
Study site
Sioux Falls, South Dakota, 57105
Study site
Springfield, Missouri, 65804
Study site
Tacoma, Washington, 98405
Study site
Winston-Salem, North Carolina, 27103
Italy7 sites
Study site
Bologna, Emilia-Romagna, 40138
Study site
Candiolo, Piedmont, 10060
Study site
Lecco, Lombardy, 23900
Study site
Milan, Lombardy, 20133
Study site
Perugia, Umbria, 06132
Study site
San Giovanni Rotondo, Apulia, 71013
Study site
Vicenza, Veneto, 36100
Germany6 sites
Study site
Bielefeld, 33604
Study site
Cologne, 50931
Study site
Frankfurt am Main, 60389
Study site
Hamburg, 20357
Study site
Mönchengladbach, 41061
Study site
Rostock, 18059
Spain5 sites
Study site
Barcelona, Barcelona, 08035
Study site
Jaén, Jaen, 23007
Study site
Lleida, Lerida, 25198
Study site
Madrid, Madrid, 28041
Study site
Madrid, Madrid, 28046
France3 sites
Study site
Besançon, 25030
Study site
Montpellier, 34298
Study site
Saint-Herblain, 44805
Russia3 sites
Study site
Moscow, 143423
Study site
Saint Petersburg, 197758
Study site
Tula, 300053
South Korea3 sites
Study site
Seoul, 110-744
Study site
Seoul, 135-710
Study site
Seoul, 138-736
About this study
Official title: A Multicenter, Multinational Phase II Study to Assess the Clinical Safety and Feasibility of Trastuzumab Emtansine Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-positive Breast Cancer
This single-arm open-label study assessed the safety, feasibility, and efficacy of trastuzumab emtansine (T-DM1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer. Patients received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.
- Conditions
- Breast Cancer
- Being tested
- 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 emtansineDrug
Also called T-DM1
Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab emtansine | Experimental | Trastuzumab emtansine 3.6 mg/kg was administered intravenously on Day 1 of each 3-week treatment cycle up to a maximum of 17 cycles. Receives: Drug: Trastuzumab emtansine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment
A cardiac event was defined as death from a cardiac cause or severe congestive failure (New York Heart Association [NYHA] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% from Baseline to an LVEF of < 50%.
Measured: Baseline to 12 weeks after the start of trastuzumab emtansine treatment
Adverse Events, LVEF Function, and Deaths
The following percentages of participants are reported: At least 1 adverse event while receiving T-DM1; at least 1 serious adverse event while receiving T-DM1; an adverse event leading to discontinuation, dose delay, or dose reduction of trastuzumab emtansine treatment; symptomatic cardiac dysfunction; and asymptomatic decline in left ventricular ejection fraction (LVEF). An asymptomatic LVEF decline was defined as a LVEF < 50% and a maximum decrease ≥ 10% from Baseline. The percentage of participants who died is reported.
Measured: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
Secondary outcomes (6)
Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Radiotherapy With Trastuzumab Emtansine Treatment
Measured: From the start to the end of concurrent radiotherapy (up to 51 weeks)
Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Hormonal Therapy With Trastuzumab Emtansine Treatment
Measured: From the start to the end of concurrent hormonal therapy (up to 51 weeks)
Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment
Participants were to receive up to a total of 17 cycles of trastuzumab emtansine. If trastuzumab was given concurrently with either the optional docetaxel or optional radiation, then the number of 3-week cycles of trastuzumab therapy was subtracted from the planned 17 cycles of trastuzumab emtansine therapy.
Measured: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
Percentage of Participants Who Completed ≥ 95% of the Planned Radiotherapy Treatment With Concurrent Trastuzumab Emtansine Administration Without Significant (> 5 Days) Delay
Measured: From the start to the end of radiotherapy treatment (up to 51 weeks)
Percentage of Participants With a Pathological Complete Response
Pathological complete response was defined as the absence of invasive neoplastic cells at microscopic examination of the primary tumor and lymph nodes after surgery following primary systemic therapy. Pathological complete response was evaluated in participants treated with neoadjuvant therapy doxorubicin/cyclophosphamide-5-fluorouracil/epirubicin/cyclophosphamide followed by 1 or more doses of trastuzumab emtansine and who underwent surgery.
Measured: Day of surgery
Disease-free Survival at Month 12
Disease-free survival was defined as the time from date of first protocol treatment for adjuvant patients or date of surgery for neoadjuvant patients to disease recurrence, occurrence of invasive contralateral breast cancer, other second primary cancer (excluding non-breast second primary), or death, whichever occurred first.
Measured: From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2010 (estimated)
- Study startOct 2010
- Primary completionJun 2013
- Study completionJun 2013
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 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01196052
- Sponsor's protocol ID
- BO22857
- Other IDs
- TDM4874g
- Status last verified
- Sep 2014
- First submitted
- 3 Sep 2010
- Last updated
- 6 Oct 2014
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L. Feasibility and cardiac safety of trastuzumab emtansine after anthracycline-based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2-positive early-stage breast cancer. J Clin Oncol. 2015 Apr 1;33(10):1136-42. doi: 10.1200/JCO.2014.58.7782. Epub 2015 Feb 23.
PubMed 25713436
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Multinational Phase II Study to Assess the Clinical Safety and Feasibility of Trastuzumab Emtansine Sequentially With Anthracycline-based Chemotherapy, as Adjuvant or Neoadjuvant Therapy for Patients With Early Stage HER2-positive Breast Cancer
- ClinicalTrials.gov ID
- NCT01196052
- Acronym / sponsor ID
- BO22857
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- Oct 2010
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 8 Sep 2010 (estimated)
- Results
- Posted 26 Jun 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This single-arm open-label study assessed the safety, feasibility, and efficacy of trastuzumab emtansine (T-DM1) after the completion of anthracycline-based adjuvant/neoadjuvant chemotherapy in patients with early HER2-positive breast cancer. Patients received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.
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 emtansineTrastuzumab emtansine 3.6 mg/kg was administered intravenously on Day 1 of each 3-week treatment cycle up to a maximum of 17 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Adult patients ≥ 18 years of age.
- Locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive breast cancer documented at a local laboratory (patients with inflammatory breast cancer must be able to have a core needle biopsy).
- Herceptin (HER)2-positive tumor, confirmed by central testing using immunohistochemistry (IHC) and in situ hybridization (ISH) methods.
- Willingness to receive anthracycline-based chemotherapy or have received doxorubicin/cyclophosphamide (AC) OR 5-fluorouracil (FU)/epirubicin/ cyclophosphamide (FEC) in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment.
- 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 should use condoms for the duration of the study. Specific country requirements will be followed.
Key exclusion criteria (13 listed)
- Stage IV breast cancer or bilateral breast cancer.
- Pregnant or breastfeeding women.
- History of other malignancy within the previous 5 years, except contralateral breast cancer and ductal carcinoma in situ (DCIS)/lobular carcinoma in situ (LCIS), appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other cancers with outcome similar to those mentioned above.
- Radiation therapy, immunotherapy, or biotherapy within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study enrollment is allowed. Patients receiving AC/FEC in a similar fashion to the study treatment prescribed for adjuvant or neoadjuvant treatment of breast cancer will be allowed to enroll in the study after the completion of their AC/FEC. No other prior history of cardiotoxic chemotherapy is allowed.
- Active cardiac history.
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 emtansineAlso: T-DM1Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial. | Drug | Trastuzumab emtansine |
Primary outcome
Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment
Time frame: Baseline to 12 weeks after the start of trastuzumab emtansine treatment
A cardiac event was defined as death from a cardiac cause or severe congestive failure (New York Heart Association [NYHA] Class III or IV) with a decrease in left ventricular ejection fraction (LVEF) of ≥ 10% from Baseline to an LVEF of < 50%.
Adverse Events, LVEF Function, and Deaths
Time frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
The following percentages of participants are reported: At least 1 adverse event while receiving T-DM1; at least 1 serious adverse event while receiving T-DM1; an adverse event leading to discontinuation, dose delay, or dose reduction of trastuzumab emtansine treatment; symptomatic cardiac dysfunction; and asymptomatic decline in left ventricular ejection fraction (LVEF). An asymptomatic LVEF decline was defined as a LVEF < 50% and a maximum decrease ≥ 10% from Baseline. The percentage of participants who died is reported.
6 secondary outcomes
Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Radiotherapy With Trastuzumab Emtansine Treatment
Time frame: From the start to the end of concurrent radiotherapy (up to 51 weeks)
Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Hormonal Therapy With Trastuzumab Emtansine Treatment
Time frame: From the start to the end of concurrent hormonal therapy (up to 51 weeks)
Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment
Time frame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
Percentage of Participants Who Completed ≥ 95% of the Planned Radiotherapy Treatment With Concurrent Trastuzumab Emtansine Administration Without Significant (> 5 Days) Delay
Time frame: From the start to the end of radiotherapy treatment (up to 51 weeks)
Percentage of Participants With a Pathological Complete Response
Time frame: Day of surgery
Disease-free Survival at Month 12
Time frame: From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 25713436Krop IE, Suter TM, Dang CT, Dirix L, Romieu G, Zamagni C, Citron ML, Campone M, Xu N, Smitt M, Gianni L. Feasibility and cardiac safety of trastuzumab emtansine after anthracycline-based chemotherapy as (neo)adjuvant therapy for human epidermal growth factor receptor 2-positive early-stage breast cancer. J Clin Oncol. 2015 Apr 1;33(10):1136-42. doi: 10.1200/JCO.2014.58.7782. Epub 2015 Feb 23.
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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.
Clinical Trials study director
Hoffmann-La Roche
44 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab emtansine in people with Breast Cancer, run by Hoffmann-La Roche at 44 sites in 8 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 9 inclusion and 13 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 6 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Italy, Germany, Spain, France and 3 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 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 26 Jun 2014). 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 a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment (time frame: Baseline to 12 weeks after the start of trastuzumab emtansine treatment). The study lists 2 primary outcomes in all. 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 NCT01196052, 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 6 Oct 2014.