A Phase II Study of Neoadjuvant Trastuzumab+Docetaxel+NPLD+/-Bevacizumab in Her2-pos. Early Breast Cancer (ABCSG 32)

May 12, 2014 updated by: Austrian Breast & Colorectal Cancer Study Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Salzburg, Austria, 5020
        • Paracelsus Medical University Salzburg-Oncology, Coop. Group
      • Vienna, Austria, 1090
        • Medical University Vienna, General Hospital
      • Vienna, Austria, 1130
        • State Hospital Vienna-Hietzing
      • Vienna, Austria, 1090
        • Med. Univ. Vienna; General Hospital Vienna
    • Styria
      • Graz, Styria, Austria, 8036
        • Medical University of Graz-Oncology; Coop. Group
      • Leoben, Styria, Austria, 8700
        • State Hospital Leoben
    • Tyrol
      • Innsbruck, Tyrol, Austria, 6020
        • Gynaegological Medical University Innsbruck
      • Kufstein, Tyrol, Austria, 6330
        • District Hospital Kufstein
    • Upper Austria
      • Linz, Upper Austria, Austria, 4010
        • Hospital BHS Linz, Coop. Study Group
      • Linz, Upper Austria, Austria, 4020
        • AKH Linz
    • Vorarlberg
      • Feldkirch, Vorarlberg, Austria, 6807
        • State Hospital Feldkirch, Coop. Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Laboratory

  • 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 1.

Concomitant Conditions

  • Other malignancy within the last 5 years before randomization except for curatively treated carcinoma in situ of the cervix or non-melanomatous skin cancer
  • Evidence of distant metastasis judged clinically and at least by chest-X-ray, liver-sonography and bone scan. If there is any clinical suspicion of brain metastasis, a CT-scan or MRI of the brain must be conducted within 4 weeks prior to randomization.

  • Serious concurrent disease which could affect compliance with the protocol or interpretation of results, including, but not limited to:

    • Active infection requiring i.v. antibiotics
    • Uncontrolled hypertension
    • Clinically significant history of cardiovascular disease as indicated by: cerebrovascular accident or stroke; myocardial infarction; unstable angina; NYHA Grade II or greater CHF; cardiac arrhythmia requiring medication; clinically significant valvular heart disease.
    • Dyspnea at rest necessitating supportive oxygen therapy or with significant pleural effusions
    • Poorly controlled diabetes mellitus
    • History or evidence upon physical/neurological examination of CNS disease unrelated to cancer (e.g. uncontrolled seizures) unless adequately treated with standard medical therapy
    • History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding
    • History of abdominal fistula, GI perforation, or intra-abdominal abscess within 6 months of randomization
    • Serious non-healing wound, peptic ulcer, or bone fracture
    • Clinically significant malabsorption syndrome, ulcerative colitis, disease affecting GI function, resection of the stomach or small bowel, or inability to take oral medication
    • Uncorrected hypokalemia or hypomagnesemia
    • Organ allografts requiring immunosuppressive therapy
  • Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect patient compliance with study routines, or place the patient at high risk from treatment related complications.
  • Known hypersensitivity to any of the study drugs/excipients.
  • Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.

Other

  • Pregnant, lactating females or women of childbearing potential without a negative pregnancy test
  • Fertile males or females of childbearing potential
  • Patients not accessible for treatment or follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: A: Trastuzumab+Docetaxel
Drug: Trastuzumab, Docetaxel

6 cycles - Day1 (Day22 = Day1): Trastuzumab: 8 mg/kg loading dose (1st cycle) i.v.; 6 mg/kg maintenance dose in subsequent cycles i.v.

Docetaxel: 100 mg/m2 by 60 min i.v. infusion

Other Names:
  • Therapy Arm A
Experimental: B: Trastuzumab+Docetaxel+Bevacizumab
Drug: Trastuzumab, Docetaxel, Bevacizumab

6 cycles - Day1 (Day22 = Day1): Trastuzumab: 8 mg/kg loading dose (1st cycle) i.v.; 6 mg/kg maintenance dose in subsequent cycles i.v.

Docetaxel: 100 mg/m2 by 60 min i.v. infusion Bevacizumab 15 mg/kg

Other Names:
  • Therapy Arm B
Experimental: C: Trastuzumab+Docetaxel+NPLD
Drug: Trastuzumab+Docetaxel+NPLD

6 cycles - Day1 (Day22=Day1): Trastuzumab: 8 mg/kg loading dose (1st cycle) i.v.; 6 mg/kg maintenance dose in subsequent cycles i.v.

Docetaxel: 75 mg/m2 by 60 min IV infusion NPLD 50 mg/m2 by 60 min i.v. infusion

Other Names:
  • Therapy Arm C
Experimental: D: Trastuzumab+Docetaxel+NPLD+Bevacizumab
Drug: Trastuzumab+Docetaxel+NPLD+Bevacizumab

6 cycles - Day1 (Day22= Day1): Trastuzumab: 8 mg/kg loading dose (1st cycle) i.v.; 6 mg/kg maintenance dose in subsequent cycles i.v.

Docetaxel: 75 mg/m2 by 60 min i.v. infusion NPLD: 50 mg/m2 by 60 min i.v. infusion; Bevacizumab 15 mg/kg

Other Names:
  • Therapy Arm D

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
between day 1 of cycle 1 and day 28 after the day of final surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (ypCR)
Time Frame: up to 22 weeks
ypCR defined as absence of invasive tumor at time of final surgery
up to 22 weeks
Total pathological complete response (ytpCR)
Time Frame: up to 22 weeks
ytpCR defined as absence of invasive tumor and tumor cells in the breast and the axillar lymphnodes (ypT0 or yDCIS and ypN=0)
up to 22 weeks
Overall clinical response rate (cORR)
Time Frame: up to 22 weeks
cORR defined as the percentage of patients with either a complete clinical response (cCR) or a partial clinical response (cPR), but no ypCR
up to 22 weeks
Safety evaluation according to patients numbers of AEs, SAEs, lab test abnormalities, cardiac assessment, clinical evaluation
Time Frame: up to 22 weeks
Safety (AEs, SAEs, lab test abnormalities, cardiac assessment, clinical evaluation)of the combination trastuzumab and docetaxel with bevacizumab and trastuzumab, docetaxel, and NPLD plus/minus bevacizumab at the time of final surgery
up to 22 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Austrian Breast & Colorectal Cancer Study Group

Collaborators

Hoffmann-La Roche
Cephalon

Investigators

  • Principal Investigator: Guenther Steger, MD, Austrian Breast & Colorectal Cancer Study Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2011

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

May 31, 2011

First Submitted That Met QC Criteria

June 3, 2011

First Posted (Estimate)

June 6, 2011

Study Record Updates

Last Update Posted (Estimate)

May 13, 2014

Last Update Submitted That Met QC Criteria

May 12, 2014

Last Verified

May 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABCSG 32
  • 2010-023324-25 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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