Multicentre Randomized Phase II Study of Neoadjuvant Trastuzumab Plus Docetaxel With and Without Bevacizumab and Trastuzumab Plus Docetaxel Plus Non-pegylated Liposome-encapsulated Doxorubicin (NPLD) With and Without Bevacizumab in HER2-positive Early Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- Trastuzumab, Docetaxel
- Conditions
- Breast Cancer
- Sponsor
- Austrian Breast & Colorectal Cancer Study Group
- Enrollment
- 100
- Locations
- 11
- Primary Endpoint
- Cardiac toxicity
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Multicenter randomised phase II study of neoadjuvant therapy in HER2 positive early breast cancer. Primary aim is to evaluate the cardiac toxicity of the combined treatment (trastuzumab, docetaxel, bevacizumab, NPLD) in comparison to the standard therapy.
Detailed Description
The target study population consists of male and female pre- and postmenopausal patients with HER2-positive, adenocarcinoma of the breast (except inflammatory breast cancer, T4d) scheduled to receive neoadjuvant cytotoxic treatment. Patients must have pathologically confirmed breast cancer with histologically confirmed HER2 over-expression. At screening, patients must have an adequate left ventricular ejection fraction (LVEF); an ECOG performance status of 0 or 1; adequate liver, renal and bone marrow function; and be free of other serious diseases that could affect protocol compliance or interpretation of results. Patients should not be at increased risk of GI perforation, hypertension, proteinuria, wound healing complications, thromboembolism or hemorrhage. Patients must not have had another primary malignancy that could affect compliance with the protocol or interpretation of results. Patients with central nervous system (CNS) metastases are excluded. Pregnant or lactating females are excluded. Patients with hypertension (\>150 mmHG systolic or \>100 mmHG diastolic) and patients with a history of GI perforation, abdominal fistula or intra-abdominal abscess within 6 months of study entry are excluded. Full anticoagulation therapy at study entry is allowed as long as the patient has been on a stable level of anticoagulants for at least 2 weeks at the time of study treatment start.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female or male, age ≥ 18 years
- •Pathologically confirmed invasive primary breast adenocarcinoma (except inflammatory breast cancer, T4d) scheduled for taxane containing neoadjuvant systemic treatment with/without palpable lymph nodes.
- •Documented HER2 protein overexpression as determined by immunohistochemistry (IHC) 3+ or by demonstrated HER2/c-erbB2 gene amplification of the primary tumor by a local laboratory.
- •LVEF ≥ 55% measured by echocardiography or MUGA within 4 weeks before randomization
- •ECOG Performance Status ≤ 1
- •Able and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- •Written Informed Consent
Exclusion Criteria
- •Current Treatment
- •Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
- •Chronic daily treatment with corticosteroids excl. inhaled steroids.
- •Chronic daily treatment with aspirin and aspirin analogs or clopidogrel
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization or anticipation of need for major surgery during the course of study treatment
- •Current or recent (within 30 days prior to randomization) treatment with another investigational drug or participation in another investigational study.
- •Inadequate bone marrow function
- •Inadequate liver function
- •Inadequate renal function
- •Patients not receiving anticoagulant medication who have activated partial thromboplastin time (aPTT) within 7 days prior to Day1 of the cycle
Arms & Interventions
A: Trastuzumab+Docetaxel
Intervention: Trastuzumab, Docetaxel
B: Trastuzumab+Docetaxel+Bevacizumab
Intervention: Trastuzumab, Docetaxel, Bevacizumab
C: Trastuzumab+Docetaxel+NPLD
Intervention: Trastuzumab+Docetaxel+NPLD
D: Trastuzumab+Docetaxel+NPLD+Bevacizumab
Intervention: Trastuzumab+Docetaxel+NPLD+Bevacizumab
Outcomes
Primary Outcomes
Cardiac toxicity
Time Frame: between day 1 of cycle 1 and day 28 after the day of final surgery
to evaluate the cardiac toxicity of the combination trastuzumab+docetaxel+bevacizumab and trastuzumab+docetaxel+NPLD +/- bevacizumab in comparison to the standard therapy, trastuzumab+docetaxel using a composite endpoint appearing between day 1 of cycle 1 and day 28 after the day of final surgery.
Secondary Outcomes
- Safety evaluation according to patients numbers of AEs, SAEs, lab test abnormalities, cardiac assessment, clinical evaluation(up to 22 weeks)
- Total pathological complete response (ytpCR)(up to 22 weeks)
- Overall clinical response rate (cORR)(up to 22 weeks)
- Pathological complete response (ypCR)(up to 22 weeks)