Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Nonmetastatic Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01093235
First received: March 24, 2010
Last updated: NA
Last verified: March 2010
History: No changes posted
  Purpose

RATIONALE: Drugs used in chemotherapy, such as docetaxel, fluorouracil, epirubicin hydrochloride, and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving combination chemotherapy together with or without bevacizumab is more effective in treating patients with nonmetastatic breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy works compared with giving combination chemotherapy together with bevacizumab in treating patients with nonmetastatic breast cancer.


Condition Intervention Phase
Breast Cancer
Cardiac Toxicity
Perioperative/Postoperative Complications
Biological: bevacizumab
Drug: cyclophosphamide
Drug: docetaxel
Drug: epirubicin hydrochloride
Drug: fluorouracil
Procedure: assessment of therapy complications
Procedure: neoadjuvant therapy
Procedure: quality-of-life assessment
Procedure: therapeutic conventional surgery
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: ARTemis - Avastin Randomized Trial With Neo-Adjuvant Chemotherapy for Patients With Early Breast Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Complete pathological response rates (tumor and lymph nodes) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Pathological complete response rate in breast alone [ Designated as safety issue: No ]
  • Radiological response after 3 and 6 courses of chemotherapy [ Designated as safety issue: No ]
  • Rate of breast conservation [ Designated as safety issue: No ]
  • Toxicities, including cardiac safety and surgical complications (wound healing, bleeding, and thrombosis) [ Designated as safety issue: Yes ]
  • Quality of life [ Designated as safety issue: No ]

Estimated Enrollment: 800
Study Start Date: April 2009
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To compare the efficacy of neoadjuvant therapy comprising docetaxel, fluorouracil, epirubicin hydrochloride, and cyclophosphamide with versus without bevacizumab in patients with HER2-negative nonmetastatic breast cancer.

Secondary

  • To assess quality of life of female patients treated with these regimens.

OUTLINE: This is a multicenter study. Patients are stratified according to age (≤ 50 years old vs > 50 years old), estrogen receptor status (negative [Allred score 0-2] vs weakly positive [Allred score 3-5] vs strongly positive [Allred score 6-8]), total tumor size* (≤ 50 mm vs > 50 mm), clinical involvement of axillary nodes (yes vs no), and inflammatory/locally advanced disease (T4) (yes vs no). Patients are randomized to 1 of 2 treatment arms.

NOTE: *In cases with multifocal disease in one breast, or bilateral disease, the size to be used for the stratification is the sum of the single largest diameter of all measurable tumors.

  • Arm I: Patients receive docetaxel IV on day 1; treatment repeats every 3 weeks for 3 courses. Patients then receive fluorouracil IV, epirubicin hydrochloride IV, and cyclophosphamide IV on day 1 (FEC). Treatment with fluorouracil, epirubicin hydrochloride, and cyclophosphamide repeats every 3 weeks for 3 courses.
  • Arm II: Patients receive bevacizumab IV over 30 to 90 minutes and docetaxel IV on day 1; treatment repeats every 3 weeks for 3 courses. Patients then receive FEC as in arm I. Treatment with FEC repeats every 3 weeks for 3 courses. Patients also receive bevacizumab IV over 30 to 90 minutes and docetaxel IV on day 1 in FEC course 1 only.

Within 3-6 weeks after completion of last dose of study therapy, patients in both arms undergo surgery. Within 4-8 weeks after surgery, patients undergo radiotherapy according to standard protocol.

Women complete quality-of-life questionnaires (FACT-B and EuroQoL) at baseline and during and after completion of study treatment.

After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed invasive breast cancer
  • HER2-negative disease

    • IHC 0/1 OR IHC 2+ and FISH negative
  • Must meet 1 of the following criteria:

    • Unifocal tumor meeting 1 of the following criteria:

      • T2 or T3 tumors (radiological size > 20 mm)
      • T4 tumor of any size with direct extension to the chest wall or the skin
      • Inflammatory carcinoma with tumor of any size
    • Multifocal tumor meeting the following criteria:

      • The sum of each tumors' maximum diameter must be ≥ 20 mm (total radiological tumor size ≥ 20 mm)
    • Other locally advanced disease meeting 1 of the following criteria:

      • Any T stage with involvement of large or fixed axillary lymph nodes (radiological diameter > 20 mm or clinical N2) and primary breast tumor of any diameter
      • Any T stage with involvement of large or fixed axillary lymph nodes (radiological diameter > 20 mm or clinical N2), without a primary breast tumor identified and the presence of breast cancer in a lymph node must be histopathologically confirmed by lymph node biopsy (tru-cut or whole lymph node)
  • Embedded paraffin tumor block available from pre-chemotherapy biopsy and surgical specimen
  • Bilateral disease allowed
  • No evidence of metastatic disease
  • No prior breast cancer except for ductal carcinoma in situ of the breast surgically cured > 10 years ago
  • Any hormone receptor status

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • WBC > 3 x 10^9/L
  • Hemoglobin > 10 g/dL
  • Platelet count > 100 x 10^9/L
  • AST/ALT ≤ 1.5 times upper limit of normal (ULN)
  • Alkaline phosphatase ≤ 2 times ULN
  • Bilirubin normal

    • Isolated elevation of bilirubin to ≤ 3 times ULN with a presumptive diagnosis of Gilbert syndrome allowed if AST/ALT and alkaline phosphatase are within normal limits
  • Creatinine ≤ 1.5 times ULN
  • PT and PTT/aPTT ≤ 1.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception
  • Must be fit to receive chemotherapy on this trial, in the opinion of the responsible clinician, as indicated by the following criteria:

    • No clinically significant cardiac abnormalities
    • No myocardial infarction within the past 6 months
    • LVEF normal (at least 50%) by MUGA scan or echocardiogram
  • No prior ischemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thromboembolic disease, cardiac failure, inflammatory bowel disease, gastroduodenal ulcer, symptomatic diverticulitis, or bleeding diathesis
  • No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg) with or without antihypertensive medication

    • Patients with initial blood pressure elevations are eligible provided initiation or adjustment of antihypertensive medication lowers pressure to meet entry criteria
  • No other previous malignancy except basal cell carcinoma, carcinoma in situ of the cervix, or ductal carcinoma in situ of the breast treated by surgery only and disease-free for 10 years
  • No concurrent medical or psychiatric problem that might prevent completion of treatment or follow-up
  • No presence of active uncontrolled infection
  • No history of nephritic or nephrotic syndrome
  • No traumatic injury within the past 28 days
  • No evidence of other disease that, in the opinion of the investigator, places the patient at high risk of treatment-related complications
  • No nonhealing wound, peptic ulcer, or bone fracture

PRIOR CONCURRENT THERAPY:

  • No prior neoadjuvant endocrine therapy
  • No prior chemotherapy or radiotherapy
  • No major surgical procedure within the past 28 days
  • No concurrent full therapeutic dose of anticoagulants or aspirin > 325 mg/day, clopidogrel > 75 mg/day, or corticosteroids
  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: NCT01093235

Locations
United Kingdom
Addenbrooke's Hospital Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Contact Person    44-1223-336-800    Hme22@cam.ac.uk   
Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Investigators
Principal Investigator: Helena Earl, MBBS, PhD, FRCP Cambridge University Hospitals NHS Foundation Trust
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01093235     History of Changes
Other Study ID Numbers: CDR0000668530, CRCA-CCTC-WCTU-ARTemis, ISRCTN68502941, EUDRACT-2008-002322-11, EU-21017, MREC-08/H1102/104
Study First Received: March 24, 2010
Last Updated: March 24, 2010
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
cardiac toxicity
perioperative/postoperative complications
HER2-negative breast cancer
male breast cancer
estrogen receptor-negative breast cancer
estrogen receptor-positive breast cancer
progesterone receptor-negative breast cancer
progesterone receptor-positive breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
inflammatory breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Postoperative Complications
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pathologic Processes
Cyclophosphamide
Fluorouracil
Docetaxel
Bevacizumab
Epirubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators

ClinicalTrials.gov processed this record on August 28, 2014