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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01367028
Recruitment Status : Completed
First Posted : June 6, 2011
Last Update Posted : May 13, 2014
Hoffmann-La Roche
Information provided by (Responsible Party):
Austrian Breast & Colorectal Cancer Study Group

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Trastuzumab, Docetaxel Drug: Trastuzumab, Docetaxel, Bevacizumab Drug: Trastuzumab+Docetaxel+NPLD Drug: Trastuzumab+Docetaxel+NPLD+Bevacizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2011
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
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 Name: 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 Name: 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 Name: 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 Name: Therapy Arm D

Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Pathological complete response (ypCR) [ Time Frame: up to 22 weeks ]
    ypCR defined as absence of invasive tumor at time of final surgery

  2. 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)

  3. 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

  4. 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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 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.


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01367028

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Medical University of Graz-Oncology; Coop. Group
Graz, Styria, Austria, 8036
State Hospital Leoben
Leoben, Styria, Austria, 8700
Gynaegological Medical University Innsbruck
Innsbruck, Tyrol, Austria, 6020
District Hospital Kufstein
Kufstein, Tyrol, Austria, 6330
Hospital BHS Linz, Coop. Study Group
Linz, Upper Austria, Austria, 4010
AKH Linz
Linz, Upper Austria, Austria, 4020
State Hospital Feldkirch, Coop. Group
Feldkirch, Vorarlberg, Austria, 6807
Paracelsus Medical University Salzburg-Oncology, Coop. Group
Salzburg, Austria, 5020
Med. Univ. Vienna; General Hospital Vienna
Vienna, Austria, 1090
Medical University Vienna, General Hospital
Vienna, Austria, 1090
State Hospital Vienna-Hietzing
Vienna, Austria, 1130
Sponsors and Collaborators
Austrian Breast & Colorectal Cancer Study Group
Hoffmann-La Roche
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Principal Investigator: Guenther Steger, MD Austrian Breast & Colorectal Cancer Study Group

Additional Information:
Publications of Results:
Amadori D, Gasparini G, Ardizzoni A, Comella G, Saracchini S, Barone C, Bordonaro R, et al. Phase II study of liposomal doxorubicin (Myocet®), docetaxel and trastuzumab combination as first line treatment of patients with HER-2/neu positive locally advanced or metastatic breast cancer. Cancer Res 2009; 69 (Suppl.): (2).January 15, 3149
Antón A, Ruiz-Simón A, Plazaola A, Calvo L, Segui M. A, Santabella A, Muňoz M, et al. Phase II study of a 3-weekly liposome-encapsulated doxorubicin/docetaxel/pegfilgrastim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER+) early stage cancer patients (II-IIIa). GEICAM 2003-03 study. Cancer Res 2009; 69 (Suppl.): (2).January 15, 5117
Avastin® (Bevacizumab) Investigator Brochure, Fifteenth Version: November 2007
Phase II trial of the anti-VEGF antibody bevacizumab in combination with vinorelbine for refractory advanced breast cancer [abstract 446]. Breast Cancer Res Treat 2002;76:S115
Epstein M, Ayala R, Tchekmedyian N et al. HER-2/neu-overexpressing human breast cancer xenografts exhibit increased angiogenic potential mediated by vascular endothelial growth factor (VEGF). Breast Cancer Res. Treat. 2002; 76: S143
Extra JM, Antoine EC, Vincent-Salomon A et al. Favourable effect of trastuzumab (Herceptin®) treatment in metastatic breast cancer patients: results from the French Hermine cohort study. Poster presentation, 2006 SABCS, San Antonio, Texas
Hambleton J, Novotny F, Hurwitz H et al. Bevacizumab (Avastin) does not increase the incidence of bleeding in patients with metastatic colorectal cancer receiving simultaneous anticoagulation. ASCO New Orleans 2004,Abstract 3528
Herceptin® (Trastuzumab) Investigator Brochure, Version: October 5, 2007
Jackisch C, Eustermann H, Schoenegg W et al. Routine clinical usage of trastuzumab (Herceptin®) in advanced breast cancer in Germany from 2001 to 2006. 2007; Poster Presentation, SABCS
Kabbinavar FF, Wong JT, Ayala RE et al. The effect of antibody to vascular endothelia growth factor and cisplatin on the growth of lung tumors in nude mice [abstract]. Proc Am Assoc Cancer Res 1995; 36:488
Ménard S (on behalf of the Demetra Group). Observational Demetra study: Survival of metastatic breast carcinoma patients after treatment with trastuzumab. J Clin Oncol 26: 2008 (May 20 suppl; abstr 1062)
Miles D, Chan A, Romieu G et al. Randomized, double-blind, placebo-controlled, phase III study of bevacizumab with docetaxel or docetaxel with placebo as first-line therapy for patients with locally recurrent or metastatic breast cancer (mBC): AVADO. J Clin Oncol 26:2008 (May 20 Suppl; abstr LBA1011). Presented at the 2008 ASCO Annual Meeting
Myers CE. Anthracyclines. In: Chabner B, ed. Pharmacologic principles of cancer treatment. Philadelphia: Saunders 1982: xii, 457 p
O'Shaughnessy J, Blackwell KL, Burstein H et al. A randomized study of lapatinib alone or in combination with trastuzumab in heavily pretreated HER2+ metastatic breast cancer progressing on trastuzumab therapy. J Clin Oncol 26: 2008 (May 20 suppl; abstr 1015)
Pegram M, Yeon C, Ku NC et al. Phase I combined biological therapy of breast cancer using two humanized monoclonal antibodies directed against HER2 protooncogene and vascular endothelial growth factor (VEGF). 2004; SABCS
Pegram M, Chan D, Dichmann RA et al., Phase II combined biological therapy targeting the HER2 proto-oncogene and the vascular endothelial growth factor using trastuzumab (T) and bevacizumab (B) as first-line treatment of HER2-amplified breast cancer. 2006; Poster Presentation, SABCS
Potchoiba MJ, West M, Smolarek TA, Macaione G, Santacroce E, Lundeen GR. Tissue distribution of doxorubicin in the free and liposomal forms in male Beagles. Proc Am Assoc Cancer Res 1996; 37:A2675
Rugo H, Dickler MN, Scott JH et al. Change in circulating endothelial cells (CEC) and tumor cells (CTC) in patients (pts) receiving bevacizumab and erlotinib for metastatic breast cancer (MBC) predicts stable disease at first evaluation [abstract 525]. J Clin Oncol 2005;23:10s
Schippinger W, Lileg B, Ploner F, Weitzer W, Bauernhofer TH, Samonigg H. Neoadjuvant chemotherapy with non-pegylated liposomal doxorubicin, docetaxel and trastuzumab in HER-2/neu overexpressing breast cancer. Ann Oncol 2007; 18 (Suppl 9): 28p
Shweiki D, Itin A, Soffer D et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature (Lond.) 1992; 359: 843-845.Slamon DJ, Clark GM, Wong SG et al. Human breast cancer: correlation of relapse and survival with amplification of the Her-2/neu oncogene. Science 1987; 235:177-182
Sledge GW, Miller KD, Moisa CF et al. Safety and efficacy of capecitabine plus bevacizumab as first-line treatment in metastatic breast cancer J Clin Oncol 2007; 25: 35s ASCO abstract 1013
Traina TA, Dickler MN, Caravelli JF et al. A phase II trial of letrozole in combination with bevacizumab, an anti-VEGF antibody, in patients with hormone receptor-positive metastatic breast cancer [abstract 2030]. Breast Cancer Res Treat 2005;94:S93
Tycznski JE, Bray F and. Parkin DM. Breast cancer in Europe. International Agency for Research on Cancer: European Network of Cancer Registries Cancer Fact Sheet 2002; 2
Von Minckwitz G, Zielinski C, Maarteense E et al. Capecitabine vs. capecitabine + trastuzumab in patients with HER2-positive metastatic breast cancer progressing during trastuzumab treatment: The TBP phase III study (GBG 26/BIG 3-05). J Clin Oncol 26: 2008 (May 20 suppl; abstr 1025)
Yardley DA, Hart L, Badarinath S et al. Preliminary results of a multicenter study of bevacizumab with 3 docetaxel-based adjuvant breast cancer regimens. San Antonio Breast Cancer Symposium, 2007, Poster Presentation

Other Publications:
Greene FL, Page DL Fleming ID et al. eds. AJCC Cancer Staging Handbook. 6th Edition. 2002; Springer
Xeloda® (Capecitabine) Investigator Brochure, 9th Version August 2007

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Responsible Party: Austrian Breast & Colorectal Cancer Study Group Identifier: NCT01367028    
Other Study ID Numbers: ABCSG 32
2010-023324-25 ( EudraCT Number )
First Posted: June 6, 2011    Key Record Dates
Last Update Posted: May 13, 2014
Last Verified: May 2014
Keywords provided by Austrian Breast & Colorectal Cancer Study Group:
HER2-positive early breast cancer
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action