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

• ClinicalTrials.gov Identifier: NCT01196052
• Recruitment Status: Completed
• First Posted: September 8, 2010
• Results First Posted: June 26, 2014
• Last Update Posted: October 6, 2014
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

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

Belgium

Bruxelles, Belgium, 1000

Wilrijk, Belgium, 2610

France

Besancon, France, 25030

Montpellier, France, 34298

Saint Herblain, France, 44805

Germany

Bielefeld, Germany, 33604

Frankfurt am Main, Germany, 60389

Hamburg, Germany, 20357

Köln, Germany, 50931

Mönchengladbach, Germany, 41061

Rostock, Germany, 18059

Italy

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

Spain

Barcelona, Spain, 08035

Jaen, Spain, 23007

Lerida, Spain, 25198

Madrid, Spain, 28041

Madrid, Spain, 28046

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT01196052
• Other Study ID Numbers: BO22857; TDM4874g ( Other Identifier: Genentech, Inc. )
• First Posted: September 8, 2010
• Results First Posted: June 26, 2014
• Last Update Posted: October 6, 2014
• Last Verified: September 2014

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Ado-Trastuzumab Emtansine; Skin Diseases; Trastuzumab; Maytansine; Antineoplastic Agents, Immunological; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Immunotoxins; Immunoconjugates; Immunologic Factors; Physiological Effects of Drugs