Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Paclitaxel; Docetaxel; Capecitabine
Intervention description: 80 mg/m^2 by vein (IV) Weekly Over 1 Hour x 12 Weeks; 75 mg/m^2 by vein (IV) Over 1 Hour Once Every 3 Weeks; 1500 mg/m^2 by mouth Twice Daily x 2 Weeks
Intervention MeSH terms: Paclitaxel; Docetaxel; Capecitabine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 603.0
Sex: Female
Healthy volunteers: No
Keywords: Breast Cancer; Capecitabine; Docetaxel; Paclitaxel; Taxotere; Taxol; Xeloda; Taxanes; Operable Breast Cancer

Summary:

      Primary Objectives:

        -  Determine the impact of each regimen on the disease free and overall survival of
           patients with operable breast cancer.

        -  Determine the ability of docetaxel/capecitabine to downstage primary breast cancer when
           administered in the neoadjuvant setting when compared with weekly paclitaxel.

        -  Determine the ability of each regimen to enhance breast conservation therapy when
           administered in the neoadjuvant setting. (See protocol text for additional objectives
           and details).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with histologic confirmation of invasive, but non-inflammatory carcinoma of
             the breast.

          2. Stage I (T1N0) are not eligible for the neo-adjuvant portion of the protocol.

          3. High-risk patients (patients with any of the following: high proliferation rate - Ki67
             >35% or poorly differentiated tumors (black's modified grade 3); ER/PR negative;
             lymphovascular invasion) with stage I disease are eligible for adjuvant therapy.

          4. Patients with pure mucinous carcinomas, tubular carcinomas or pure medullary
             carcinomas are eligible if the patient's tumor is larger than 3 cm in size or if the
             patient has tumor involvement of the lymph nodes (>2mm).

          5. Patients with bilateral breast cancers are eligible.

          6. Patients with pN2a (metastasis in four to nine axillary lymph nodes) are eligible as
             are patients with pN3a (ten or more axillary lymph nodes). Patients with
             infraclavicular lymph node involvement are NOT eligible.

          7. Patients must have clinically measurable disease to be treated in the neoadjuvant
             setting. This includes patients with a non-palpable primary who have histologically
             proven lymph node (LN) involvement that is clinically palpable and measurable by
             ultrasound

          8. Histologic confirmation of invasive tumor will be done by core needle biopsy for
             patients with intact primary tumors. If patients have undergone adequate core biopsy
             prior to evaluation at MDACC, repeat core biopsy is optional.

          9. Patients must sign an informed consent indicating that they are aware of the
             investigational nature of the study, in keeping with institutional policy.

         10. Patients with a prior history of breast cancer are eligible if the current primary
             breast cancer is of a higher stage than the original breast cancer and the patient has
             not received any of the current study medications including past doxorubicin.

         11. Patients should have adequate bone marrow function, as defined by peripheral
             granulocyte count of > 1,500/mm3, and platelet count > 100,000/mm3. Patients must have
             adequate liver function with a bilirubin within normal laboratory values.
             Transaminases (SGPT) may be up to 2.5x upper limit of normal (ULN) if alkaline
             phosphatase is < ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are
             < ULN.

         12. In addition, patients should have adequate renal function, defined as a serum
             creatinine < 2.5 mg% and/or creatinine clearance greater than 51 ml/min as calculated
             by Cockcroft and Gault Equation: Cockcroft and Gault Equation: Creatinine clearance
             for males = {(140 - age [yrs])(body weight [kg])}/{(72) (serum creatinine [mg/dL])}.
             Creatinine clearance for females = 0.85 x male value

         13. Patients who had surgical therapy prior to referral will be eligible for randomization
             to systemic chemotherapy administered in the adjuvant setting.

         14. Patients who have overexpression of the her-2/neu oncogene are eligible for the study.

        Exclusion Criteria:

          1. Patients with N2 (clinical staging) or N3 (clinical staging) nodal disease,
             inflammatory breast cancer, or metastatic disease are not eligible. This includes
             patients with infraclavicular and/or supraclavicular lymph node involvement. Patients
             with pN2a (metastasis in four to nine axillary lymph nodes) are eligible.

          2. Patients with pN2b (metastasis in clinically apparent internal mammary lymph nodes in
             the absence of axillary lymph node metastasis) are not eligible. Patients with T4
             lesions in the neoadjuvant setting are not eligible. Patients with limited T4 lesions
             in the adjuvant setting (for example, focal extension into the skin with negative
             margins) are eligible.

          3. Severe hypersensitivity reactions to agents formulated in either cremophor or
             polysorbate 80 must be excluded. Patients with hypersensitivity reactions to any of
             the study medications must be excluded.

          4. Those patients with history of other malignancies will be excluded, except
             non-melanoma skin cancer and non-invasive cervical cancer.

          5. Patients with uncompensated congestive heart failure are not eligible. Patients with
             myocardial infarction within the past 12 months are ineligible.

          6. Patients who are pregnant or lactating are not eligible. Women of childbearing
             potential must have a negative pregnancy test prior to initiation of chemotherapy.
             Women of childbearing potential who will not use a reliable and appropriate
             contraceptive method during the study are not eligible.

          7. Patients who have had an organ allograft are ineligible.

          8. Patients with serious concurrent infections are ineligible.

          9. Sexually active male patients unwilling to practice contraception during the study are
             ineligible.

         10. Patients with pre-existing peripheral neuropathy > grade 1.