A Phase Ib/II, open-label study of the safety, tolerability, and efficacy of trastuzumab-MCC-DM1 in combination with pertuzumab administered intravenously to patients with HER2-positive locally advanced or metastatic breast cancer who have progressed while receiving prior therapy

Phase 1

• Conditions: Treatment in patients with HER2-overexpressing locally advanced or metastatic breast cancer; MedDRA version: 9.1Level: LLTClassification code 10027475Term: Metastatic breast cancer; MedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer

• Registration Number: EUCTR2008-008276-14-FR
• Lead Sponsor: F. Hoffmann-la Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-03-24
• Study Completion: 2011-07-25
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

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

• 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified