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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01196052
Recruitment Status : Completed
First Posted : September 8, 2010
Results First Posted : June 26, 2014
Last Update Posted : October 6, 2014
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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. Patients received T-DM1 3.6 mg/kg intravenously on Day 1 of each 3-week cycle, for up to 17 cycles.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab emtansine Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 153 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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%.

  2. 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.

Secondary Outcome Measures :
  1. 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) ]
  2. 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) ]
  3. 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.

  4. 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) ]
  5. 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.

  6. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT01196052

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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
Russian Federation
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
Sponsors and Collaborators
Hoffmann-La Roche
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche Identifier: NCT01196052    
Other Study ID Numbers: BO22857
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Ado-Trastuzumab Emtansine
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs