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A Phase II Clinical Trial of Four Cycles of Doxorubicin andCyclophosphamide Followed by Weekly Paclitaxel GivenConcurrently With Pazopanib as Neoadjuvant Therapy Followedby Postoperative Pazopanib for Women With Locally AdvancedBreast Cancer

Phase 2
18 Years
Open (Enrolling)
Neoplasms, Breast

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Trial Information

A Phase II Clinical Trial of Four Cycles of Doxorubicin andCyclophosphamide Followed by Weekly Paclitaxel GivenConcurrently With Pazopanib as Neoadjuvant Therapy Followedby Postoperative Pazopanib for Women With Locally AdvancedBreast Cancer

This is a phase II non-randomized, multi-center study aimed to evaluate the efficacy and
safety of the combination of pazopanib and paclitaxel following treatment with
cyclophosphamide and doxorubicin for the treatment of neoadjuvant breast cancer.

Patients will receive standard doses of AC every 21 days for 4 cycles. This will be followed
by weekly paclitaxel 80 mg/m2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given
concurrently with pazopanib 800 mg PO daily starting with the first paclitaxel dose and
continuing until 7 days before surgery. Clinical complete response rate will be determined
by tumor assessments performed by palpation at two time points: following AC (before
paclitaxel/pazopanib begins) and 2-4 weeks following the last dose of paclitaxel (before
surgery). Following recovery from preoperative therapy, patients will undergo the
clinically-indicated surgery. Pazopanib will resume 4-6 weeks after surgery and continue
daily for 6 months of postoperative pazopanib therapy.

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

- 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

- 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

- 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

- Any sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement

- 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

- 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

- Sensory/motor neuropathy greater or equal to grade 2, as defined by the NCI's CTCAE

- 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.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes

Outcome Description:

pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy.

Outcome Time Frame:

From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



Canada: Health Canada

Study ID:




Start Date:

July 2009

Completion Date:

April 2013

Related Keywords:

  • Neoplasms, Breast
  • Neoadjuvant Breast Cancer
  • Pazopanib (GW786034)
  • NSABP Foundation, Inc.
  • cyclophosphamide
  • Paclitaxel
  • Doxorubicin
  • Breast Neoplasms
  • Neoplasms



GSK Investigational Site Bakersfield, California  93309
GSK Investigational Site Gainesville, Florida  32610
GSK Investigational Site Duluth, Minnesota  55805
GSK Investigational Site Raleigh, North Carolina  27609
GSK Investigational Site Fort Worth, Texas  76104
GSK Investigational Site Green Bay, Wisconsin  54301
GSK Investigational Site Bettendorf, Iowa  52722
GSK Investigational Site Royal Oak, Michigan  48073
GSK Investigational Site Pittsburgh, Pennsylvania  15213
GSK Investigational Site Salem, Virginia  24153
GSK Investigational Site Birmingham, Alabama  35209
GSK Investigational Site Aurora, Colorado  80012
GSK Investigational Site Edison, New Jersey  08837
GSK Investigational Site Oregon City, Oregon  97045
GSK Investigational Site Seattle, Washington  98133