Treatment in patients with HER2-overexpressing locally advanced or metastatic breast cancer MedDRA version: 9.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer MedDRA version: 9.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer
Conditions
Interventions
Product Name: trastuzumab-MCC-DM1 (TDM-1)
Product Code: RO5304020/F02-01
Pharmaceutical Form: Powder for concentrate for solution for infusion
CAS Number: 1018448-65-1
Current Sponsor code: RO5304020
Sponsors
F. Hoffmann-la Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed Informed Consent Form • Age = 18 years • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 • Histologically documented breast cancer • Locally advanced or metastatic breast cancer that has progressed on the patient’s most recent prior regimen - For the purposes of this study, locally advanced breast cancer is defined as unresectable local or regional disease that has previously been treated with radiation therapy, chemotherapy, and HER2-directed therapy. • HER2-positive breast cancer documented as fluorescence in situ hybridization (FISH)-positive, immunohistochemistry (IHC) 3 + or chromogenic in situ hybridization (CISH)-positive by local laboratory assessment • Tumor tissue blocks or 15-20 unstained tissue slides for confirmatory central laboratory HER2 status testing and other exploratory assessments • Prior trastuzumab in any line of therapy • Prior chemotherapy combined with HER2-targeted therapy for locally advanced or metastatic disease • No prior T-DM1 or pertuzumab therapy • Measurable disease, defined as at least one lesion = 2 cm on computed tomography (CT) scan or = 1 cm on spiral CT scan • Cardiac ejection fraction = 55% by either ECHO or MUGA scan • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to first study treatment: - Absolute neutrophil count = 1500 cells/mm3 - Platelet count = 100,000 cells/mm3 - Hemoglobin = 9.0 g/dL - Albumin = 2.5 g/dL - Total bilirubin = 1.5 × ULN - SGOT (AST) and SGPT (ALT) = 2.5 × ULN, with the following exception: Patients with documented liver metastases: AST and/or ALT = 5 × ULN - Serum creatinine = 1.5 mg/dL, or creatinine clearance = 50 mL/min based on Cockroft-Gault glomerular filtration rate (GFR) estimation: - (140 - age) × (weight in kg) × (0.85 if female)/72 × serum creatinine • For women of childbearing potential, agreement to use an effective form of contraception (patient and/or partner [e.g., surgical sterilization, a reliable barrier method, birth control pills, or contraceptive hormone implants]), and to continue its use for the duration of the study • Life expectancy = 90 days Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Less than 21 days since the last anti-tumor therapy, including chemotherapy, biologic, experimental, immune, hormonal or radiotherapy for the treatment of breast cancer, with the following exceptions: - Hormone-replacement therapy or oral contraceptives - Palliative radiation therapy involving = 25% of marrow-bearing bone within 14 days prior to first study treatment • History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued • Peripheral neuropathy of Grade = 2 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 3.0, at the time of, or within 3 weeks prior to, the first study therapy • History of exposure to the following cumulative doses of anthracyclines: - Doxorubicin > 500 mg/m2 (or the relevant equivalent dose of another anthracycline) - Liposomal doxorubicin > 900 mg/m2 - Epirubicin > 720 mg/m2 • History of clinically significant cardiac dysfunction, including: - Current uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg), or unstable angina - History of symptomatic CHF (Grade > 3 by NCI CTCAE or Class > II by New York Heart Association [NYHA] criteria, or serious cardiac arrhythmia requiring treatment, with the exceptions of atrial fibrillation and paroxysmal supraventricular tachycardia - History of myocardial infarction within 6 months prior to first study treatment - Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy • Current known active infection with HIV, hepatitis B virus, or hepatitis C virus • Pregnancy or lactation • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease) • Major surgical procedure or significant traumatic injury within 28 days prior to first study treatment, or anticipation of the need for major surgery during the course of study treatment • Symptomatic hypercalcemia requiring use of bisphosphonate therapy at the time of, or within 21 days of, the first study treatment - Patients who are receiving bisphosphonate therapy specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. • Brain metastases that are either: - Untreated or - Require any type of therapy (including radiation, surgery, or steroids) to control symptoms from brain metastases within 60 days of the first study treatment. • History of other malignancy within the last 5 years, except for appropriately treated carcinoma in situ of the cervix, basal cell carcinoma, or synchronous or subsequent HER2-positive breast cancer or other malignancy with a similar expected curative outcome
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To characterize the safety and tolerability of the combination of T-DM1 and pertuzumab administered every 3 weeks to patients with HER2-positive locally advanced or metastatic breast cancer who have previously received trastuzumab in any line of therapy, have received chemotherapy combined with HER2-targeted therapy for advanced disease, and have progressed while receiving their most recent therapy • To evaluate the pharmacokinetics of T-DM1 when the combination of T-DM1 and pertuzumab is administered on this schedule • To make a preliminary assessment of the efficacy of the combination of T-DM1 and pertuzumab administered on this schedule, as measured by objective response rate based on investigator assessment using modified RECIST, Version 1.0;Secondary Objective: • To estimate the PFS of patients who receive the combination of T-DM1 and pertuzumab administered on this schedule • To assess the duration of response of the combination of T-DM1 and pertuzumab administered on this schedule • To assess the development of anti-therapeutic antibodies to T-DM1;Primary end point(s): Phase Ib - Safety of co-administration of TDM-1 + pertuzumab Phase II - Investigator assessed objective response, defined as a complete or partial response determined on two consecutive occasions =4 weeks apart. The primary analysis for efficacy and safety will be conducted around 1 year after the completion of patient enrollment or at study termination, whichever happens first. | — |
Countries
Belgium, France, Germany
Outcome results
None listed