A Study Comparing Combinations of Chemotherapy for Treating Women who have Undergone Surgery for Node-Positive Breast Cancer

Overview

  • Study type

    Interventional
  • Study phase

    III
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Scottsdale/Phoenix, Arizona: 05-004349
    • Jacksonville, Florida: 05-004349
    NCT ID: NCT00093795
    Sponsor Protocol Number: B-38

About this study

The purpose of this study is to compare three different combination chemotherapy regimens and evaluate how well they work in treating women who have undergone surgery for node-positive breast cancer. Drugs used in chemotherapy, such as docetaxel, doxorubicin, cyclophosphamide, paclitaxel, and gemcitabine work in different ways to stop tumor cells from dividing so they stop growing or die. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

This study is ongoing, but not recruiting participants

Inclusion Criteria

  • Must consent to participate in the study and sign an approved consent form conforming with federal and institutional guidelines
  • Must have a life expectancy of at least 10 years and a Zubrod performance status of 0 or 1
    • Comorbid conditions but not the diagnosis of breast cancer should be taken into consideration when determining life expectancy
  • The interval between the last surgery for breast cancer staging or treatment and randomization must be no more than 84 days
  • The tumor must be invasive carcinoma of the breast on histologic examination
  • All of this staging criteria must be met
    • By clinical and pathologic evaluation, primary tumor must be T1-3
    • By clinical evaluation, ipsilateral nodes must be cN0, cN1, or cN2a
    • By pathologic evaluation, ipsilateral nodes must be pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b
      • Only if due to microscopic involvement of internal mammary node detected by sentinel lymph node dissection and with more than 3 positive axillary lymph nodes
  • Must have an estrogen receptor analysis performed on the primary tumor prior to randomization
    • If negative, then progesterone receptor  analysis must be performed
    • If positive, PgR analysis is desired, but not mandatory
    • "Marginal" or "borderline" results will be considered positive regardless of the methodology used
  • Must have had either a lumpectomy or a total mastectomy
  • Must have completed one of the following procedures for evaluation of pathologic nodal status
    • Sentinel lymphadenectomy followed by removal of additional non-sentinel lymph nodes
      • This approach is strongly recommended
    • Sentinel lymphadenectomy alone if one of the following criteria is met
      • Pathologic nodal staging based on sentinel lymphadenectomy is pN1mi or pN1b
      • Surgeon elects not to remove additional non-sentinel nodes
        • This approach is strongly discouraged, but will not preclude participation in B-38
    • Axillary lymphadenectomy without sentinel node isolation procedure
  • Must have no clinical or radiologic evidence of metastatic disease
  • Has either skeletal pain or alkaline phosphatase that is greater than ULN but less than or equal to 2.5 x ULN, if bone scans fail to demonstrate metastatic disease
    • Suspicious findings on bone scan must be confirmed as benign by x-ray, MRI, or biopsy
  • Has aspartate transaminase or alkaline phosphatase greater than ULN, if liver imaging fails to demonstrate metastatic disease and the following requirements are met at the time of randomization
    • Postoperative absolute granulocyte count (AGC) must be greater than or equal to 1200/mm3
    • Postoperative platelet count must be greater than or equal to 100,000/mm3
    • Postoperative evidence of adequate hepatic function must be met
      • Total bilirubin must be less than or equal to ULN for the lab unless has a grade 1 bilirubin elevation (greater than ULN to 1.5 x ULN) due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin
      • Alkaline phosphatase must be less than or equal to 2.5 x ULN for the lab
      • AST must be less than or equal to 1.5 x ULN for the lab
      • Alkaline phosphatase and AST cannot both be greater than ULN
    • Postoperative serum creatinine must be less than or equal to ULN
  • At the time of randomization, must have had 
    • History and physical exam, EKG, and imaging of chest within past 3 months
    • Bilateral mammogram within the past 6 months
  • Within 3 months prior to entry, must have a baseline left ventricular ejection fraction, measured by Multiple Gated Acquisition (MUGA) scan or echocardiogram, greater than or equal to lower limit of normal (LLN) for the facility performing the procedure and no evidence of regional wall abnormalities
  • A history of non-breast malignancies if they have been disease-free for 5 or more years prior to randomization and are deemed by their physician to be at low risk for recurrence
  • The following are eligible if diagnosed and treated within the past 5 years
    • Carcinoma in situ of the cervix
    • Carcinoma in situ of the colon
    • Melanoma in situ
    • Basal cell and squamous cell carcinoma of the skin
  • Special conditions for eligibility of lumpectomy patients
    • Radiation therapy and surgery
      • Generally, lumpectomy should be reserved for tumors less than 5 cm
      • At the investigator's discretion,  lumpectomy for tumors greater than or equal to 5 cm is eligible if criteria for lumpectomy is met
      • Margins of the resected specimen must be histologically free of invasive tumor and DCIS as determined by the local pathologist
      • If pathologic examination demonstrates tumor present at the line of resection, additional operative procedures may be performed to obtain clear margins
      • This is permissible even if axillary evaluation has been completed
      • Tumor still present at the resected margin after re-excision(s) must undergo total mastectomy to be eligible
        • Margins positive for lobular carcinoma in situ are eligible without additional resection
      • Irradiation of regional lymph nodes is optional, but plans for radiation therapy must be declared by the investigator prior to randomization for stratification purposes
  • Special conditions for eligibility of mastectomy patients
    • Radiation therapy 
      • Postmastectomy chest wall and/or regional nodal irradiation is optional.
      • Plans for radiation in mastectomy must be declared by the investigator prior to randomization for stratification purposes

Exclusion Criteria

  • Males
  • Females with the following conditions or prior therapies
    • Tumor that has been determined to be human epidermal growth factor receptor 2 (HER2)-positive by immunohistochemistry (3+) or by fluorescent in situ hybridization (positive for gene amplification)
    • Contralateral breast cancer (invasive or DCIS)
    • A mass or mammographic abnormality in the opposite breast suspicious for malignancy unless there is biopsy proof that the mass is not malignant
    • Primary tumor staged as T4 for any reason
    • Clinical nodal stages including cN2b and cN3 or pathologic nodal stages including pN0(i+), pN2b, pN3b with clinically apparent internal mammary nodes, or pN3c
    • Suspicious nodes in the contralateral axilla or suspicious supraclavicular nodes unless there is biopsy evidence that they are not involved with tumor
    • Prior history of breast cancer, including DCIS 
      • A history of LCIS is eligible
    • Treatment, including radiation therapy, chemotherapy, and/or hormonal therapy administered for the currently diagnosed breast cancer prior to randomization
      • Exception is hormonal therapy, which may have been given for up to a total of 28 days anytime after diagnosis and before study entry
        • Hormonal therapy must stop at or before randomization and be re-started, if indicated, following chemotherapy
      • Another exception is radiation therapy if enrolled in NSABP B-39 and assigned to partial breast irradiation (Group 2) 
        • May have had Radiation therapy prior to B-38 study entry
    • Prior therapy with anthracyclines or taxanes for any malignancy
    • Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement therapy, etc. 
      • Are eligible if this therapy is discontinued prior to randomization
    • Therapy with any hormonal agents such as raloxifene (Evista®), tamoxifen, or other selective estrogen-receptor modulators (SERMs), either for osteoporosis or breast cancer prevention
      • Eligible only if these medications are discontinued prior to randomization
    • Cardiac disease that would preclude the use of anthracyclines, including
      • A history of myocardial infarction documented by elevated cardiac enzymes or regional wall abnormalities on assessment of left ventricular  function
      • Angina pectoris that requires the use of anti-anginal medication
      • Any history of documented congestive heart failure
      • Serious cardiac arrhythmia requiring medication
      • Severe conduction abnormality
      • Valvular disease with documented cardiac function compromise
      • Uncontrolled hypertension defined as blood pressure greater than 160/100 on antihypertensive therapy
    • Conditions that would prohibit administration of corticosteroids
    • Sensory/motor neuropathy greater than or equal to grade 2, as defined by the NCI's Common Terminology Criteria for Adverse Events Version 3.0
    • Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude a patient from receiving any of the treatment options or would prevent prolonged follow-up
    • History of hepatitis B or C
    • Pregnancy or lactation at the time of proposed randomization
      • Females of reproductive potential must agree to use an effective non-hormonal method of contraception
    • Concurrent treatment with other investigational agents for the treatment of breast cancer.
    • Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude meeting the study requirements
  • Special conditions for ineligibility of lumpectomy patients
    • Radiation therapy and surgery
      • Less than whole breast radiation
      • Diffuse tumors (as demonstrated on mammography) treated with lumpectomy
        • Eligible if they undergo mastectomy
      • Treated with lumpectomy and there is another clinically dominant mass or mammographically suspicious abnormality within the ipsilateral breast remnant
        • Such a mass must be biopsied and demonstrated to be histologically benign prior to randomization or, if malignant, must be surgically removed with clear margins
      • The margins of the resected specimen are involved with invasive tumor or DCIS

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Donald Northfelt, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

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CLS-20314045

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