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
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|ClinicalTrials.gov Identifier: NCT01196052|
Recruitment Status : Completed
First Posted : September 8, 2010
Results First Posted : June 26, 2014
Last Update Posted : October 6, 2014
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|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Trastuzumab emtansine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||153 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2010|
|Actual Primary Completion Date :||June 2013|
|Actual Study Completion Date :||June 2013|
Experimental: Trastuzumab emtansine
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.
Drug: Trastuzumab emtansine
Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial.
Other Name: T-DM1
- 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.
- 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) ]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.
- 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 ]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.
- 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 ]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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01196052
|United States, Florida|
|Fort Myers, Florida, United States, 33916|
|United States, Indiana|
|Lafayette, Indiana, United States, 47905|
|United States, Maine|
|Scarborough, Maine, United States, 04074|
|United States, Maryland|
|Kensignton, Maryland, United States, 20895|
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02115|
|Boston, Massachusetts, United States, 02130|
|United States, Missouri|
|Springfield, Missouri, United States, 65804|
|United States, Nebraska|
|Omaha, Nebraska, United States, 68114|
|United States, New York|
|Lake Success, New York, United States, 11042|
|United States, North Carolina|
|Durham, North Carolina, United States, 27710|
|Winston-Salem, North Carolina, United States, 27103|
|United States, South Dakota|
|Sioux Falls, South Dakota, United States, 57105|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|San Antonio, Texas, United States, 78258|
|United States, Washington|
|Tacoma, Washington, United States, 98405|
|Bruxelles, Belgium, 1000|
|Wilrijk, Belgium, 2610|
|Besancon, France, 25030|
|Montpellier, France, 34298|
|Saint Herblain, France, 44805|
|Bielefeld, Germany, 33604|
|Frankfurt am Main, Germany, 60389|
|Hamburg, Germany, 20357|
|Köln, Germany, 50931|
|Mönchengladbach, Germany, 41061|
|Rostock, Germany, 18059|
|Bologna, Emilia-Romagna, Italy, 40138|
|Lecco, Lombardia, Italy, 23900|
|Milano, Lombardia, Italy, 20133|
|Candiolo, Piemonte, Italy, 10060|
|San Giovanni Rotondo, Puglia, Italy, 71013|
|Perugia, Umbria, Italy, 06132|
|Vicenza, Veneto, Italy, 36100|
|Korea, Republic of|
|Seoul, Korea, Republic of, 110-744|
|Seoul, Korea, Republic of, 135-710|
|Seoul, Korea, Republic of, 138-736|
|Moscow, Russian Federation, 143423|
|Saint-Petersburg, Russian Federation, 197758|
|Tula, Russian Federation, 300053|
|Barcelona, Spain, 08035|
|Jaen, Spain, 23007|
|Lerida, Spain, 25198|
|Madrid, Spain, 28041|
|Madrid, Spain, 28046|
|Study Director:||Clinical Trials||Hoffmann-La Roche|
|Responsible Party:||Hoffmann-La Roche|
|Other Study ID Numbers:||
TDM4874g ( Other Identifier: Genentech, Inc. )
|First Posted:||September 8, 2010 Key Record Dates|
|Results First Posted:||June 26, 2014|
|Last Update Posted:||October 6, 2014|
|Last Verified:||September 2014|
Neoplasms by Site
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs