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

NCT01196052 | Completed Phase 2 Results

• 2 other identifiers: BO22857TDM4874g
• Study Type: interventional
• Target: 153
• Locations: 8 countries
• Sites: 44

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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%.

  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.

  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

  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

  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

  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

  From the start to the end of radiotherapy treatment (up to 51 weeks)

• Percentage of Participants With a Pathological Complete Response

  Day of surgery

Study Arms (1)

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.

Drug: Trastuzumab emtansine

Interventions

Trastuzumab emtansine DRUG

Trastuzumab emtansine was provided as a single-use lyophilized formulation in a glass vial.

Also known as: T-DM1

Trastuzumab emtansine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (44)

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Fort Myers, Florida, 33916, United States

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Lafayette, Indiana, 47905, United States

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Scarborough, Maine, 04074, United States

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Kensignton, Maryland, 20895, United States

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Boston, Massachusetts, 02115, United States

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Boston, Massachusetts, 02130, United States

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Springfield, Missouri, 65804, United States

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Omaha, Nebraska, 68114, United States

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Lake Success, New York, 11042, United States

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Durham, North Carolina, 27710, United States

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Winston-Salem, North Carolina, 27103, United States

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Sioux Falls, South Dakota, 57105, United States

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Nashville, Tennessee, 37203, United States

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San Antonio, Texas, 78258, United States

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Tacoma, Washington, 98405, United States

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Brussels, 1000, Belgium

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Wilrijk, 2610, Belgium

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Besançon, 25030, France

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Montpellier, 34298, France

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Saint-Herblain, 44805, France

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Bielefeld, 33604, Germany

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Cologne, 50931, Germany

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Frankfurt am Main, 60389, Germany

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Hamburg, 20357, Germany

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Mönchengladbach, 41061, Germany

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Rostock, 18059, Germany

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San Giovanni Rotondo, Apulia, 71013, Italy

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Bologna, Emilia-Romagna, 40138, Italy

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Lecco, Lombardy, 23900, Italy

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Milan, Lombardy, 20133, Italy

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Candiolo, Piedmont, 10060, Italy

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Perugia, Umbria, 06132, Italy

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Vicenza, Veneto, 36100, Italy

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Moscow, 143423, Russia

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Saint Petersburg, 197758, Russia

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Tula, 300053, Russia

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Seoul, 110-744, South Korea

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Seoul, 135-710, South Korea

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Seoul, 138-736, South Korea

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Barcelona, Barcelona, 08035, Spain

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Jaén, Jaen, 23007, Spain

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Lleida, Lerida, 25198, Spain

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Madrid, Madrid, 28041, Spain

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Madrid, Madrid, 28046, Spain

Location

Related Publications (1)

• 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.

  PMID: 25713436 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2010
• First Posted: September 8, 2010
• Study Start: October 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: October 6, 2014
• Results First Posted: June 26, 2014

Record last verified: 2014-09

Locations

US (15); IT (7); DE (6); KR (3); BE (2); ES (5); FR (3); RU (3)