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

NCT ID: NCT01196052

Last Updated: 2014-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 153 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-10-31
• Study Completion Date: 2013-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Trastuzumab emtansine

Intervention Type: DRUG

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

Interventions

Trastuzumab emtansine

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

Intervention Type: DRUG

Other Intervention Names

T-DM1

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Fort Myers, Florida, United States

Lafayette, Indiana, United States

Scarborough, Maine, United States

Kensignton, Maryland, United States

Boston, Massachusetts, United States

Boston, Massachusetts, United States

Springfield, Missouri, United States

Omaha, Nebraska, United States

Lake Success, New York, United States

Durham, North Carolina, United States

Winston-Salem, North Carolina, United States

Sioux Falls, South Dakota, United States

Nashville, Tennessee, United States

San Antonio, Texas, United States

Tacoma, Washington, United States

Brussels, , Belgium

Wilrijk, , Belgium

Besançon, , France

Montpellier, , France

Saint-Herblain, , France

Bielefeld, , Germany

Cologne, , Germany

Frankfurt am Main, , Germany

Hamburg, , Germany

Mönchengladbach, , Germany

Rostock, , Germany

San Giovanni Rotondo, Apulia, Italy

Bologna, Emilia-Romagna, Italy

Lecco, Lombardy, Italy

Milan, Lombardy, Italy

Candiolo, Piedmont, Italy

Perugia, Umbria, Italy

Vicenza, Veneto, Italy

Moscow, , Russia

Saint Petersburg, , Russia

Tula, , Russia

Seoul, , South Korea

Seoul, , South Korea

Seoul, , South Korea

Barcelona, Barcelona, Spain

Jaén, Jaen, Spain

Lleida, Lerida, Spain

Madrid, Madrid, Spain

Madrid, Madrid, Spain

Countries

United States; Belgium; France; Germany; Italy; Russia; South Korea; Spain

References

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.

Reference Type: DERIVED

PMID: 25713436 (View on PubMed)

Other Identifiers

TDM4874g

Identifier Type: OTHER

Identifier Source: secondary_id

BO22857

Identifier Type: -

Identifier Source: org_study_id