Clinical trial NCT01196052: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-09-08
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Percentage of Participants With a Cardiac Event Within 12 Weeks After the Start of Trastuzumab Emtansine Treatment
timeFrame: Baseline to 12 weeks after the start of trastuzumab emtansine treatment
measure: Adverse Events, LVEF Function, and Deaths
timeFrame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
Secondary outcomes:
measure: Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Radiotherapy With Trastuzumab Emtansine Treatment
timeFrame: From the start to the end of concurrent radiotherapy (up to 51 weeks)
measure: Percentage of Participants Who Experienced at Least 1 Adverse Event During Concurrent Hormonal Therapy With Trastuzumab Emtansine Treatment
timeFrame: From the start to the end of concurrent hormonal therapy (up to 51 weeks)
measure: Percentage of Participants Who Completed the Planned Duration of Trastuzumab Emtansine Treatment
timeFrame: From the start to the end of trastuzumab emtansine treatment (up to 51 weeks)
measure: Percentage of Participants Who Completed ≥ 95% of the Planned Radiotherapy Treatment With Concurrent Trastuzumab Emtansine Administration Without Significant (> 5 Days) Delay
timeFrame: From the start to the end of radiotherapy treatment (up to 51 weeks)
measure: Percentage of Participants With a Pathological Complete Response
timeFrame: Day of surgery
measure: Disease-free Survival at Month 12
timeFrame: From the start of trastuzumab emtansine for adjuvant patients and from the date of surgery for neoadjuvant patients to 12 months later
Other outcomes:
Locations:
city: Fort Myers
country: United States
state: Florida
city: Lafayette
country: United States
state: Indiana
city: Scarborough
country: United States
state: Maine
city: Kensignton
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Springfield
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Lake Success
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Sioux Falls
country: United States
state: South Dakota
city: Nashville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
city: Tacoma
country: United States
state: Washington
city: Bruxelles
country: Belgium
city: Wilrijk
country: Belgium
city: Besancon
country: France
city: Montpellier
country: France
city: Saint Herblain
country: France
city: Bielefeld
country: Germany
city: Frankfurt am Main
country: Germany
city: Hamburg
country: Germany
city: Köln
country: Germany
city: Mönchengladbach
country: Germany
city: Rostock
country: Germany
city: Bologna
country: Italy
state: Emilia-Romagna
city: Lecco
country: Italy
state: Lombardia
city: Milano
country: Italy
state: Lombardia
city: Candiolo
country: Italy
state: Piemonte
city: San Giovanni Rotondo
country: Italy
state: Puglia
city: Perugia
country: Italy
state: Umbria
city: Vicenza
country: Italy
state: Veneto
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Moscow
country: Russian Federation
city: Saint-Petersburg
country: Russian Federation
city: Tula
country: Russian Federation
city: Barcelona
country: Spain
city: Jaen
country: Spain
city: Lerida
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.