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

U.S. FDA Resources

Estimated Enrollment:	100
Study Start Date:	June 2011
Estimated Study Completion Date:	September 2014
Estimated Primary Completion Date:	September 2014 (Final data collection date for primary outcome measure)

Detailed 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

Austrian Breast & Colorectal Cancer Study Group

Hoffmann-La Roche

Cephalon

ABCSG official website 

HER2-positive early breast cancer

Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Doxorubicin Docetaxel Trastuzumab Bevacizumab

Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors