A multicenter, multinational phase II study to assess the clinical safety and feasibility of T-DM1 sequentially with anthracyline-based chemotherapy, as adjuvant or neoadjuvant therapy for patients with early stage HER2-positive breast cancer.
- Conditions
- Treatment of HER2 positive adjuvant or neoadjuvant therapyMedDRA version: 12.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer
- Registration Number
- EUCTR2010-019752-50-DE
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 135
• Patients with locally advanced, inflammatory, or early stage, unilateral, and histologically confirmed invasive (adenocarcinoma) breast cancer documented at a local laboratory. Patients with inflammatory breast cancer must be able to have a core needle biopsy.
• HER2-positive tumor, defined as IHC 3 + and/or FISH positive and prospectively confirmed by Sponsor-designated central laboratory, prior to study enrollment
• Willingness to receive anthracycline-based chemotherapy or have received
doxorubicin/cyclophosphamide OR 5-FU/epirubicin/cyclophosphamide in a similar dose and schedule as described in the protocol as part of neoadjuvant or adjuvant treatment
• Willingness to submit tissue blocks and/or slides from surgical specimens for
exploratory biomarker testing
• Written, informed consent indicating understanding of and willingness to participate in the study
• Age = 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
• For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly effective, non-hormonal form of contraception or two 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 3 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the study. Specific country requirements will be followed (e.g., in the United Kingdom, women of childbearing potential and male subjects and their partners of childbearing potential must use two methods of contraception [one of which must be a barrier method] for the duration of the study).
• Negative results of serum pregnancy test (human chorionic gonadotropin [HCG] pregnancy test) for premenopausal women of reproductive capacity and for women < 12 months after menopause
• Absolute neutrophil count (ANC) = 1000/µL and platelet count = 100,000/µL;
hemoglobin > 9.0 g/dL
• Total bilirubin must be <1.0 times the institutional upper limit of normal (ULN); transaminases (AST/ALT) may be =1.5 times the institutional ULN.
• Alkaline phophatase =1.5 x ULN
• Serum creatinine = 1.5 x ULN
• Patients may enroll before or after AC/FEC chemotherapy has completed.
AC/FEC chemotherapy if administered pre-enrollment must have been given.
In a similar schedule and dosing (within 20% dose recommended) as prescribed in this protocol. AC/FEC for adjuvant patients should have started within 60 days of surgery.
• Baseline LVEF by MUGA/ECHO at or above 55% if anthracycline therapy for
adjuvant/neoadjuvant treatment has not yet been given
Patients are allowed to enroll after anthracycline therapy if the LVEF was similarly
measured by MUGA/ECHO within 60 days prior to the start of AC/FEC, the baseline (pre-T-DM1) LVEF is at or above 50%, the LVEF has not decreased by more than 15% absolute points compared with the pre-AC/FEC LVEF, and if the patient has had no significant symptoms related to LV dysfunction, cardiac ischemia, or arrhythmia while or since receiving AC/FEC.
In an asymptomatic” patient if, on the post-anthracycline MUGA/ECHO, (1) the LVEF increased or stayed the same as seen on baseline MUGA/ECHO or (2) the LVEF decreased by = 15% absolute” points but is still at or above 50%. They will not be allowed to enroll an asymptomatic” patient if, at post-anthracycline MUGA/ECHO, (1) the LVEF is below 50% or (2) the LVEF decreased by = 16% absolu
• 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, 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 (including prior HER2-directed
therapy) within 5 years before study enrollment; non-cardiotoxic chemotherapy for malignancy treated > 5 years before study enrollment is allowed (e.g., non-AC
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.
• Active cardiac history, including: patients with unstable angina (change in
medications and increasing chest pain in the previous 3 months), CHF within the previous 12 months, or a history of a myocardial infarction within 12 months; patients with high-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias that are not adequately rate controlled); patients with clinically significant valvular disease; patients with uncontrolled hypertension (systolic blood pressure > 170 mm Hg and/or diastolic blood pressure > 100 mm Hg), but patients may be re-screened after medications have been given to control the hypertension
• Concurrent medical conditions, which, in the judgment of the investigator, would make them inappropriate candidates for study enrollment; this includes patients with known infection with HIV and HCV
• Current chronic daily treatment with oral corticosteroids or equivalent
• Known hypersensitivity to any of the study drugs or derivatives, including murine proteins
• Patients with severe dyspnea at rest or requiring supplementary oxygen therapy
• Active, unresolved infections at screening
• Grade = 2 peripheral neuropathy at baseline
• Major surgery within 4 weeks before enrollment that is unrelated to the breast cancer
• Patients for whom concomitant radiotherapy + T-DM1 may be contraindicated (e.g., has a connective tissue disorder that would predispose the patient to radiation toxicity or complications) yet radiation therapy is planned
• Patients assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol, including the study follow-up period
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method