Randomized Phase III, Double-Blind, Placebo-Controlled Multicenter Trial of Everolimus in Combination with Trastuzumab and Paclitaxel, as First Line Therapy in Women with HER2 Positive Locally Advanced or Metastatic Breast Cancer
- Conditions
- HER2+ locally advanced or metastatic breast cancerMedDRA version: 9.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancer
- Registration Number
- EUCTR2008-006556-21-GR
- Lead Sponsor
- ovartis Pharma Service AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 717
? Written informed consent must be obtained prior to any study-related procedures.
? Women =18 years old.
? Patients with an ECOG performance status of 0-1.
? Histologically or cytologically confirmed invasive breast carcinoma with local
recurrence or radiological evidence of metastatic disease. Local disease must
not be amenable to resection with curative intent.
? Patients fulfilling one of the following criteria are eligible to participate in this
study:
• Patients with measurable disease as per RECIST criteria.
• Patients with bone lesions, lytic or mixed (lytic + sclerotic), in the absence of measurable disease as defined by RECIST criteria.
? HER2+ patients by local laboratory testing (IHC 3+ staining or in situ
hybridization positive).
? Patients fulfilling one of the following criteria are eligible to participate in this study:
• Patient never treated with trastuzumab
• Prior trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment is discontinued > 12 months prior to randomization
? Prior treatment for breast cancer with endocrine therapy (adjuvant or metastatic settings) is allowed but should be discontinued at randomization. Patients treated with bisphosphonates at entry or who start bisphosphonates during study may continue this therapy during protocol treatment.
? Documentation of negative pregnancy test for patients of child bearing potential prior to enrollment within 7 days prior to randomization. Sexually active pre-
menopausal patients must use adequate contraceptive measures while on study.
? Patients must meet the following laboratory criteria within 21 days prior to
randomization:
• Hematology:
• Neutrophil count of = 1.5 10 9/L
• Platelet count of =100 x10 9/L
• Hemoglobin = 90 g/L
• Biochemistry:
• AST/SGOT and ALT/SGPT = 2.5 x upper limit of normal (ULN) (or < 5.0 x ULN
if the transaminase elevation is due to hepatic metastasis).
• Total serum bilirubin = 1.5 x ULN [Patients with Gilbert Syndrome must
have total bilirubin < 3ULN].
• INR = 2 x ULN
• Fasting serum cholesterol = 300 mg/dl or 7.75 mmol/L and fasting
triglycerides = 2.5 x ULN (with lipid-lowering drugs permitted)
• Serum creatinine = 1.5 x ULN
? Left ventricular ejection fraction assessment (echocardiogram or MUGA scan)
performed within 4 weeks prior to randomization, showing a LVEF value = LLN
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
? Prior mTOR inhibitors for the treatment of cancer.
? Anticancer therapy for locally advanced or metastatic breast cancer except for prior hormonal therapy. Patients who had a recurrence within 12 months weeks after end of trastuzumab and/or chemotherapy (taxanes included) as neo-adjuvant or adjuvant treatment prior to randomization are not eligible.
? Patients with only non-measurable lesions other than bone metastasis (e.g.
pleural effusion, ascites, etc.).
? Patients who have received radiotherapy to = 25% of the bone marrow within
the last 4 weeks prior to randomization; local radiotherapy is allowed.
? History of central nervous system metastasis.
? Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral everolimus.
? Active ulceration of the upper gastrointestinal tract.
? NCI Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 peripheral
neuropathy = grade 2 at randomization.
? Active cardiac disease:
•Angina pectoris that requires the use of anti-anginal medication,
•Ventricular arrhythmias except for benign premature ventricular contractions,
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication,
• Conduction abnormality requiring a pacemaker,
• Valvular disease with documented compromise in cardiac function,
• Symptomatic pericarditis.
? History of cardiac dysfunction including any one of the following:
• Myocardial infarction .
• History of documented congestive heart failure (New York Heart Association functional classification III-IV),
• Documented cardiomyopathy.
? Uncontrolled hypertension or history of poor compliance with an antihypertensive
regimen.
? Known human immunodeficiency virus infection (HIV).
? Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or
chronic restrictive pulmonary disease including dyspnoea at rest from any cause)
that could cause unacceptable safety risks or compromise compliance with the
protocol.
? Known hypersensitivity to any protocol treatment.
? Requirement for therapeutic doses of warfarin or equivalent.
? Clinically significant third space fluid accumulation.
? Pregnant (i.e., positive beta-human chorionic gonadotropin test) or breast feeding.
? Patients with other significant disease or disorders that, in the investigator’s
opinion, would exclude the patient from the study.
? Patients with inability to grant a reliable informed consent.
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