Treatment With Pazopanib for Neoadjuvant Breast Cancer
Condition: Neoplasms, Breast
MeSH terms: Breast Neoplasms
Intervention: doxorubicin + cyclophosphamide; paclitaxel + pazopanib; surgery; pazopanib monotherapy
Intervention description: 4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.; 4 cycles of paclitaxel + pazopanib; neoadjuvant surgery for breast cancer; 6 months of treatment with pazopanib monotherapy
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 101.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Neoadjuvant Breast Cancer; Pazopanib (GW786034); NSABP Foundation, Inc.; cyclophosphamide; Paclitaxel; Doxorubicin

Summary:

      The purpose of this study is to determine whether the treatment of a doxorubicin in
      combination with cyclophosphamide followed by a combination of pazopanib in combination with
      paclitaxel prior to surgery results in a pathological complete response in females with
      breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The patient must have consented to participate and must have signed and dated an
             appropriate IRB-approved consent form that conforms to federal and institutional
             guidelines for the study treatment and submission of tumor and blood samples required
             for the FB-6 correlative science studies

          -  The ECOG performance status must be 0 or 1

          -  Patients must have the ability to swallow oral medication.

          -  The diagnosis of invasive adenocarcinoma of the breast must have been made by core
             needle biopsy or limited incisional biopsy.

          -  Patients must have ER analysis performed on the primary tumor prior to randomization.
             If ER analysis is negative, then PgR analysis must also be performed. (Patients are
             eligible with either hormone receptor-positive or hormone receptor-negative tumors.)

          -  Patients must have clinical stage IIIA, IIIB, or IIIC disease with a mass in the
             breast or axilla measuring at least 2.0 cm by physical exam, unless the patient has
             inflammatory breast cancer, in which case measurable disease by physical exam is not
             required.

          -  Adequate organ function

          -  LVEF assessment by 2-D echocardiogram or MUGA scan performed within 3 months prior to
             study entry must be greater or equal to 50% regardless of the facility's LLN.

          -  ECG performed within 4 weeks before study entry must demonstrate a QTc interval that
             is less than or equal to 0.47 seconds.

          -  The TSH level must be within normal limits for the laboratory.

        Exclusion Criteria:

          -  Tumor that has been determined to be HER2-positive by immunohistochemistry (3+) or by
             FISH or CISH (positive for gene amplification), or has been determined to be
             HER2-equivocal and the investigator plans to administer trastuzumab or other targeted
             therapy.

          -  FNA alone to diagnose the primary breast cancer.

          -  Excisional biopsy or lumpectomy performed prior to study entry.

          -  Surgical axillary staging procedure prior to study entry.

          -  Definitive clinical or radiologic evidence of metastatic disease.

          -  History of ipsilateral invasive breast cancer regardless of treatment or ipsilateral
             DCIS treated with RT.

          -  Contralateral invasive breast cancer at any time.

          -  Non-breast malignancies unless the patient is considered to be disease-free for 5 or
             more years prior to study entry and is deemed by her physician to be at low risk for
             recurrence. Patients with the following cancers 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, and basal cell and squamous cell carcinoma of the skin.

          -  Requirement for chronic use of any of the prohibited medications or substances

          -  Previous therapy with anthracyclines, taxanes, or pazopanib for any malignancy.

          -  Treatment including RT, chemotherapy, and/or targeted therapy, administered for the
             currently diagnosed breast cancer prior to study entry.

          -  Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other
             SERM.

          -  Any sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement
             therapy

          -  History of hepatitis B or C.

          -  Symptomatic pancreatitis or asymptomatic greater or equal to grade 2 elevation of
             amylase or lipase as per NCI CTCAE v3.0.

          -  History of documented pancreatitis.

          -  Uncontrolled hypertension defined as systolic BP greater than 140 mmHg or diastolic BP
             greater greater than 90 mmHg, with or without anti-hypertensive medication.

          -  History of hypertensive crisis or hypertensive encephalopathy.

          -  Cardiac disease that would preclude the use of any of the drugs included in the FB-6
             treatment regimen.

          -  History of TIA or CVA.

          -  History of any arterial thrombotic event within 12 months prior to study entry.

          -  Pulmonary embolism or DVT within 6 months prior to study entry.

          -  Symptomatic peripheral vascular disease.

          -  Any significant bleeding within 6 months prior to study entry, exclusive of
             menorrhagia in premenopausal women.

          -  Known bleeding diathesis, coagulopathy, or requirement for therapeutic doses of
             coumadin.

          -  Serious or non-healing wound, skin ulcers, or bone fracture.

          -  Gastroduodenal ulcer(s) determined by endoscopy to be active.

          -  History of GI perforation, abdominal fistulae, or intra-abdominal abscess.

          -  Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of
             the stomach or small bowel, or other disease significantly affecting gastrointestinal
             function.

          -  Sensory/motor neuropathy greater or equal to grade 2, as defined by the NCI's CTCAE
             v3.0.

          -  Conditions that would prohibit intermittent administration of corticosteroids for
             paclitaxel premedication.

          -  Anticipation of need for major surgical procedures (other than the required breast
             surgery) during the course of study therapy and for at least 3 months following the
             last dose of pazopanib.

          -  Pregnancy or lactation at the time of study entry.

          -  Other nonmalignant systemic disease that would preclude the patient from receiving
             study treatment or would prevent required follow-up.

          -  Known immediate or delayed hypersensitivity reaction to doxorubicin, cyclophosphamide,
             paclitaxel, pazopanib, or drugs chemically related to pazopanib.

          -  Use of any investigational agent within 4 weeks prior to enrollment in the study.