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

This study has been completed.
Sponsor:
Collaborators:
Hoffmann-La Roche
Cephalon
Information provided by (Responsible Party):
Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier:
NCT01367028
First received: May 31, 2011
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Breast Cancer
Drug: Trastuzumab, Docetaxel
Drug: Trastuzumab, Docetaxel, Bevacizumab
Drug: Trastuzumab+Docetaxel+NPLD
Drug: Trastuzumab+Docetaxel+NPLD+Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Austrian Breast & Colorectal Cancer Study Group:

Primary Outcome Measures:
  • Cardiac toxicity [ Time Frame: between day 1 of cycle 1 and day 28 after the day of final surgery ] [ Designated as safety issue: Yes ]
    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:
  • Pathological complete response (ypCR) [ Time Frame: up to 22 weeks ] [ Designated as safety issue: No ]
    ypCR defined as absence of invasive tumor at time of final surgery

  • Total pathological complete response (ytpCR) [ Time Frame: up to 22 weeks ] [ Designated as safety issue: No ]
    ytpCR defined as absence of invasive tumor and tumor cells in the breast and the axillar lymphnodes (ypT0 or yDCIS and ypN=0)

  • Overall clinical response rate (cORR) [ Time Frame: up to 22 weeks ] [ Designated as safety issue: No ]
    cORR defined as the percentage of patients with either a complete clinical response (cCR) or a partial clinical response (cPR), but no ypCR

  • Safety evaluation according to patients numbers of AEs, SAEs, lab test abnormalities, cardiac assessment, clinical evaluation [ Time Frame: up to 22 weeks ] [ Designated as safety issue: Yes ]
    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


Enrollment: 100
Study Start Date: June 2011
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01367028

Locations
Austria
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
AKH Linz
Linz, Upper Austria, Austria, 4020
Hospital BHS Linz, Coop. Study Group
Linz, Upper Austria, Austria, 4010
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
Cephalon
Investigators
Principal Investigator: Guenther Steger, MD Austrian Breast & Colorectal Cancer Study Group
  More Information

Additional Information:
Publications:
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
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
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)
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
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)

Responsible Party: Austrian Breast & Colorectal Cancer Study Group
ClinicalTrials.gov Identifier: NCT01367028     History of Changes
Other Study ID Numbers: ABCSG 32, 2010-023324-25
Study First Received: May 31, 2011
Last Updated: May 12, 2014
Health Authority: Austria: Federal Office for Safety in Health Care

Keywords provided by Austrian Breast & Colorectal Cancer Study Group:
HER2-positive early breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Bevacizumab
Docetaxel
Doxorubicin
Liposomal doxorubicin
Trastuzumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on October 20, 2014