Trial record 1 of 1 for:    E5103
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Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
North Central Cancer Treatment Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00433511
First received: February 8, 2007
Last updated: March 26, 2014
Last verified: November 2013

February 8, 2007
March 26, 2014
November 2007
September 2016   (final data collection date for primary outcome measure)
Disease-free survival (DFS) [ Time Frame: From the date of randomization to the date of first treatment failure, assessed up to 15 years ] [ Designated as safety issue: No ]
Disease-free survival (DFS)
Complete list of historical versions of study NCT00433511 on ClinicalTrials.gov Archive Site
  • Overall survival [ Time Frame: From randomization to date of death, assessed up to 15 years ] [ Designated as safety issue: No ]
    The comparison between arms will be made using a stratified log rank test among all randomized patients.
  • Adverse events graded using the NCI CTCAE version 3.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
  • Quality of life patients in terms of physical symptoms, physical functioning, psychological state and social functioning [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
    Compared between arms using a two-sided t-test. The Wilcoxon Rank Sum test will be used to compare the arms if the distributions of scores are not normally distributed. Longitudinal modeling will be used to look at changes in the scores over time across arms.
  • Efficacy of short-term vs long-term bevacizumab, in terms of DFS
  • Overall survival
Not Provided
Not Provided
 
Doxorubicin, Cyclophosphamide, and Paclitaxel With or Without Bevacizumab in Treating Patients With Lymph Node-Positive or High-Risk, Lymph Node-Negative Breast Cancer
A Double-Blind Phase III Trial of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Bevacizumab or Placebo in Patients With Lymph Node Positive and High Risk Lymph Node Negative Breast Cancer

This randomized phase III trial studies doxorubicin, cyclophosphamide, and paclitaxel to see how well they work with or without bevacizumab in treating patients with lymph node-positive or high-risk, lymph node-negative breast cancer. Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Bevacizumab may also stop the growth of breast cancer by blocking blood flow to the tumor. Giving chemotherapy together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether doxorubicin, cyclophosphamide, and paclitaxel are more effective with or without bevacizumab in treating breast cancer.

PRIMARY OBJECTIVES:

I. To compare the disease-free survival (DFS) of patients with lymph node-positive and high risk lymph node negative breast breast cancer randomized to treatment with either doxorubicin/cyclophosphamide plus placebo followed by paclitaxel (AC + placebo > T + placebo) or the same chemotherapy regimen plus bevacizumab.

SECONDARY OBJECTIVES:

I. To compare short-term (20-24 weeks) versus long-term (50-54 weeks) bevacizumab therapy.

II. To compare the overall survival. III. To evaluate toxicity. IV. To evaluate the association between outcomes (disease-free survival, overall survival and toxicities) and genotype (derived from candidate single nucleotide polymorphisms and genome wide evaluations).

V. To compare quality of life of breast cancer patients treated with AC/Paclitaxel and bevacizumab or placebo, in terms of physical symptoms, physical functioning, psychological state and social functioning over an 18 month period. (QOL closed as of 05/28/10) VI. To determine the impact of theoretical biomarker information on patients' willingness to accept the toxicities of bevacizumab for the estimated potential benefit.

VII. To create a biospecimen repository including plasma, serum and CellSearch cassettes containing circulating tumor cells (CTC) for evaluating determinants of late relapse, including candidate biomarkers reflecting occult tumor burden (e.g., CTCs and plasma tumor deoxyribonucleic acid [DNA]) and host factors (e.g., estrogen, insulin-insulin-like growth factor [IGF] axis, inflammation, etc).

VIII. To create a biorepository of metastatic tumor samples in patients who have had a late relapse.

XV. To determine body mass index (BMI) and comorbidity burden in patients with operable breast cancer five or more years after diagnosis.

X. To determine whether there is a relationship between late relapse and BMI at diagnosis and at 5 years after diagnosis, and whether BMI-associated inflammatory and/or metabolic biomarkers are associated with early and late recurrence.

OUTLINE: This is a randomized, partially double-blind, placebo-controlled, partially open-label, multicenter study. Patients are stratified according to planned dose schedule of doxorubicin hydrochloride and cyclophosphamide (every 3 weeks vs every 2 weeks). Patients are further stratified according to estrogen receptor status (positive vs negative), lymph node involvement (node-negative vs 1-3 positive node[s] vs >= 4 positive nodes), and received/planned treatment (lumpectomy and whole breast radiation therapy vs lumpectomy and accelerated partial-breast radiation therapy [before or after chemotherapy] vs mastectomy without radiation therapy vs mastectomy [with local or regional]). Patients are randomized to 1 of 3 treatment arms (20% of patients are randomized to Arm I, 40% to Arm II, and 40% to Arm III).

ARM I: Patients receive doxorubicin hydrochloride intravenously (IV), cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.

ARM II: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.

ARM III: Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Beginning 2 months later, patients then receive open-label bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.

In all arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients complete quality of life (QOL) questionnaires followed by telephone QOL interviews at baseline and periodically. (QOL closed as of 05/28/10)

After completion of study treatment, patients are followed periodically for up to 15 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Male Breast Cancer
  • Stage IA Breast Cancer
  • Stage IB Breast Cancer
  • Stage II Breast Cancer
  • Stage IIIA Breast Cancer
  • Stage IIIB Breast Cancer
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Biological: bevacizumab
    Given IV
    Other Names:
    • anti-VEGF humanized monoclonal antibody
    • anti-VEGF monoclonal antibody
    • Avastin
    • rhuMAb VEGF
  • Other: placebo
    Given IV
    Other Name: PLCB
  • Active Comparator: Arm I
    Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV over 20-30 minutes, and placebo IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel IV over 1 hour on days 1, 8, and 15 and placebo IV over 30-90 minutes on day 1. Treatment with paclitaxel and placebo repeats every 3 weeks for 4 courses.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Other: placebo
  • Experimental: Arm II
    Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Biological: bevacizumab
  • Experimental: Arm III
    Patients receive doxorubicin hydrochloride and cyclophosphamide as in arm I and bevacizumab as in arm II. Treatment repeats every 2 or 3 weeks for 4 courses. Beginning 3 weeks later, patients then receive paclitaxel as in arm I and bevacizumab as in arm II. Treatment with paclitaxel and bevacizumab repeats every 3 weeks for 4 courses. Beginning 2 months later, patients then receive open-label bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab alone repeats every 3 weeks for 10 courses.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: paclitaxel
    • Biological: bevacizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
4950
Not Provided
September 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed adenocarcinoma of the breast at significant risk of distant recurrence based on at least one of the following criteria:

    • Involvement of at least one sentinel or axillary lymph node on routine histologic examination; patients with negative sentinel nodes and negative axillary nodes or involvement only demonstrated by immunohistochemistry are not eligible unless they meet one of the other eligibility criteria below
    • Estrogen receptor (ER) negative tumor >= 1 cm
    • ER+ tumor >= 5 cm regardless of recurrence score
    • ER+ tumor >= 1 cm but < 5 cm with a recurrence score >= 11; (patients enrolled in the TAILORx trial are eligible)
  • Patients must have completed definitive breast surgery including total mastectomy and axillary dissection (modified radical mastectomy), total mastectomy and sentinel node biopsy, breast conservation surgery and axillary dissection or breast conservation surgery and sentinel node biopsy
  • Margins of breast conservation surgery or mastectomy must be histologically free of invasive breast cancer and ductal carcinoma in situ (DCIS); patients with resection margins positive for lobular carcinoma in situ (LCIS) are eligible
  • Time from last surgery for breast cancer (breast conservation surgery, mastectomy, sentinel node biopsy, axillary dissection or re-excision of breast conservation surgery margins) to planned treatment start date must be > 28 days and =< 84 days
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Absolute neutrophil count >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3
  • Total bilirubin =< 1.5 mg/dL
  • Aspartate transferase (AST) =< 2 times upper limit of normal(ULN)
  • Serum creatinine =< 1.5 mg/dL
  • Urine protein:creatinine ratio < 1.0 or 24-hour protein
  • Partial thromboplastin time (PTT) =< 1.5 times ULN
  • Left ventricle ejection fraction (LVEF) >= institutional limits of normal by echocardiogram (ECHO) or multigated acquisition scan (MUGA)
  • Patients who have undergone breast conservation surgery must receive radiation; prior to randomization, the investigator must specify the planned radiation technique:

    • Whole breast radiation (WBRT) after chemotherapy
    • Accelerated partial breast radiation (APBI) after chemotherapy
    • Accelerated partial breast radiation (APBI) prior to chemotherapy
  • Post-mastectomy radiation therapy (RT) is required for all patients with a primary tumor of >= 5 cm or involvement of 4 or more lymph nodes; post-mastectomy RT may be administered at the investigator's discretion for all other mastectomy patients
  • Patients with human epidermal growth factor receptor (HER)2 + (3+ by immunohistochemistry [IHC] or fluorescent in situ hybridisation [FISH] ratio >= 2) breast cancer are not eligible
  • Patients with synchronous bilateral breast cancer (diagnosed within one month) are eligible if the higher TNM stage tumor meets the eligibility criteria for this trial
  • Patients must not have clinical evidence of inflammatory disease or fixed axillary nodes at diagnosis
  • Patients must not have received prior cytotoxic chemotherapy or hormonal therapy for this breast cancer; prior treatment with an anthracycline, anthracenedione or taxane for any condition is not allowed
  • Patients must not have had any major surgical procedure within 28 days of planned treatment start date
  • Patients may not have had placement of a vascular access device within 24 hours of planned Day 1 of treatment
  • Patients must not have clinically significant cardiovascular or cerebrovascular disease, including:

Any history of

  • Cerebrovascular disease including transient ischemic attack (TIA), stroke or subarachnoid hemorrhage
  • Ischemic bowel within the last 12 months
  • Myocardial infarction
  • Unstable angina
  • New York Heart Association (NYHA) class II or greater congestive heart failure
  • Grade II or greater peripheral vascular disease
  • Uncontrolled hypertension defined as systolic blood pressure (SBP) > 160 or diastolic blood pressure (DBP) > 90
  • Uncontrolled or clinically significant arrhythmia

    • Patients who require full-dose anticoagulation may enroll provided they meet the following criteria:
  • The patient must have an in-range International Normalized Ratio (INR) (usually between 2 and 3) on a stable dose of warfarin or be on stable dose of low molecular weight (LMW) heparin
  • The patient must not have active bleeding or pathological conditions that carry high risk of bleeding (e.g. varices)

    • Patients must not have a bleeding diathesis, hereditary or acquired bleeding disorder or coagulopathy
    • Patients must not have a non-healing wound or fracture; patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization are not eligible
    • Patients must not have hypersensitivity to paclitaxel or drugs using the vehicle Cremophor, Chinese hamster ovary cell products or other recombinant human antibodies
    • Women must not be pregnant or breast-feeding due to the potential harmful effects of bevacizumab on the developing fetus; all females of childbearing potential must have a blood or urine test within 7 days prior to randomization to rule out pregnancy
    • Women of childbearing potential and sexually active males must use an accepted and effective method of contraception
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Peru,   South Africa
 
NCT00433511
NCI-2009-00561, NCI-2009-00561, U10CA021115, ECOG-E5103, CDR0000528955, E5103, E5103, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
  • North Central Cancer Treatment Group
  • Cancer and Leukemia Group B
  • Eastern Cooperative Oncology Group
Principal Investigator: Kathy Miller Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP