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

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-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: 60

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
- For the purposes of this study, locally advanced breast cancer is defined as unresectable local or regional disease.
• 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
• Confirmed availability (prior Day 1) of tumor tissue blocks or 15-20 unstained tissue slides at screening for confirmatory central laboratory HER2 status testing and other exploratory assessments. Tissue specimens must be submitted within 60 days after the first dose of study drug.
• Second or later line patients must have relapsed following or progressed on HER2-directed therapy.
• 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 study enrollment (defined as the day the patient is assigned a subject number [not a screening number] via IVRS):
- Absolute neutrophil count = 1500 cells/mm3
- Platelet count = 100,000 cells/mm3
- Hemoglobin = 9.0 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 and men with partners of childbearing potential, agreement to use a highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner, and to continue the use of contrception for the duration of the study treatment and for at least 6 months after the last dose of study treatment. Male patients whose partners are pregnant should use condoms for the duration of the pregnancy.
• Life expectancy = 90 days as assessed by the investigator
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 is allowed if administred =14 days prior to first study treatment
• History of intolerance or hypersensitivity to trastuzumab and/or adverse events related to trastuzumab, murine proteins, or any of the exipients 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 listed below. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not of exceed the equivalent of 500 mg/m² of docorubicin, using the conversion factors provided in Appendix F. The medical monitor should be consulted if there are Questions.
- Doxorubicin > 500 mg/m2 (or the 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 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)
- Patients with severe dyspnea at rest, due to complications of advanced malignancy,
or requiring supplementary oxygen therapy are also excluded.
• 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 for painful bony metastases or to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.
• Brain metastases that:
- Are Untreated or
- Are progressive, or
Have required 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, non-melanoma skin carcinoma, or other malignancy with a similar expected curative outcome

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

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