Clinical Trials /

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

NCT01093235

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Nonmetastatic Breast Cancer
  • Official Title: ARTemis - Avastin Randomized Trial With Neo-Adjuvant Chemotherapy for Patients With Early Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CDR0000668530
  • SECONDARY ID: CRCA-CCTC-WCTU-ARTemis
  • SECONDARY ID: ISRCTN68502941
  • SECONDARY ID: EUDRACT-2008-002322-11
  • SECONDARY ID: EU-21017
  • SECONDARY ID: MREC-08/H1102/104
  • NCT ID: NCT01093235

Conditions

  • Breast Cancer
  • Cardiac Toxicity
  • Perioperative/Postoperative Complications

Interventions

DrugSynonymsArms
bevacizumab
cyclophosphamide
docetaxel
epirubicin hydrochloride
fluorouracil

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete pathological response rates (tumor and lymph nodes)
Time Frame:
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Disease-free survival
Time Frame:
Safety Issue:
Description:
Measure:Overall survival
Time Frame:
Safety Issue:
Description:
Measure:Pathological complete response rate in breast alone
Time Frame:
Safety Issue:
Description:
Measure:Radiological response after 3 and 6 courses of chemotherapy
Time Frame:
Safety Issue:
Description:
Measure:Rate of breast conservation
Time Frame:
Safety Issue:
Description:
Measure:Toxicities, including cardiac safety and surgical complications (wound healing, bleeding, and thrombosis)
Time Frame:
Safety Issue:
Description:
Measure:Quality of life
Time Frame:
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Cambridge University Hospitals NHS Foundation Trust

Trial Keywords

  • 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

Last Updated

March 24, 2010