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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01196052
• Other study ID #: BO22857
• Secondary ID: TDM4874g
• Status: Completed
• Phase: Phase 2
• First received: September 3, 2010
• Last updated: September 26, 2014
• Start date: October 2010
• Est. completion date: June 2013

Study information

• Verified date: September 2014
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 153
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Belgium,  France,  Germany,  Italy,  Korea, Republic of,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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)	Yes
Secondary	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)	Yes
Secondary	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)	Yes
Secondary	Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment	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.	From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)	No
Secondary	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)	No
Secondary	Percentage of Participants With a Pathological Complete Response	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.	Day of surgery	No
Secondary	Disease-free Survival at Month 12	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.	From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later	No