Treatment With Pazopanib for Neoadjuvant Breast Cancer

NCT ID: NCT00849472

Last Updated: 2014-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2013-04-30

Brief 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.

Detailed Description

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.

Conditions

Neoplasms, Breast

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Arm

Preoperative

Cycles 1-4 Doxorubicin 60 mg/m2 IV over 15 minutes + Cyclophosphamide 600 mg/m2 IV over 30 minutes of Day 1 every 21 days

followed by:

Cycles 5-8 Paclitaxel 80 mg/m2 IV over 60 minutes (Days 1, 8, and 15) every 28 days in combination with pazopanib (800 mg) PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning on Day 1 of the first paclitaxel cycle Until 7 days before surgery

Followed by Surgery

Postoperative Pazopanib 800 mg PO once daily (2 tablets taken at the same time each day either 1 hour before or 2 hours after a meal) Daily beginning 4-6 weeks after surgery 6 months from first postoperative dose

Group Type: EXPERIMENTAL

doxorubicin + cyclophosphamide

Intervention Type: DRUG

4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.

paclitaxel + pazopanib

Intervention Type: DRUG

4 cycles of paclitaxel + pazopanib

surgery

Intervention Type: PROCEDURE

neoadjuvant surgery for breast cancer

pazopanib monotherapy

Intervention Type: DRUG

6 months of treatment with pazopanib monotherapy

Interventions

doxorubicin + cyclophosphamide

4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.

Intervention Type: DRUG

paclitaxel + pazopanib

4 cycles of paclitaxel + pazopanib

Intervention Type: DRUG

surgery

neoadjuvant surgery for breast cancer

Intervention Type: PROCEDURE

pazopanib monotherapy

6 months of treatment with pazopanib monotherapy

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

NSABP Foundation Inc

NETWORK

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Decatur, Alabama, United States

GSK Investigational Site

Huntsville, Alabama, United States

GSK Investigational Site

Huntsville, Alabama, United States

GSK Investigational Site

Antioch, California, United States

GSK Investigational Site

Fremont, California, United States

GSK Investigational Site

Hayward, California, United States

GSK Investigational Site

Oakland, California, United States

GSK Investigational Site

Redwood City, California, United States

GSK Investigational Site

Richmond, California, United States

GSK Investigational Site

Roseville, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

Sacramento, California, United States

GSK Investigational Site

San Francisco, California, United States

GSK Investigational Site

San Jose, California, United States

GSK Investigational Site

San Rafael, California, United States

GSK Investigational Site

Santa Clara, California, United States

GSK Investigational Site

Santa Rosa, California, United States

GSK Investigational Site

South San Francisco, California, United States

GSK Investigational Site

Stockton, California, United States

GSK Investigational Site

Vacaville, California, United States

GSK Investigational Site

Vallejo, California, United States

GSK Investigational Site

Walnut Creek, California, United States

GSK Investigational Site

Colorado Springs, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

Englewood, Colorado, United States

GSK Investigational Site

Greeley, Colorado, United States

GSK Investigational Site

Lafayette, Colorado, United States

GSK Investigational Site

Wheat Ridge, Colorado, United States

GSK Investigational Site

Wheat Ridge, Colorado, United States

GSK Investigational Site

Fernandina Beach, Florida, United States

GSK Investigational Site

Gainesville, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Jacksonville, Florida, United States

GSK Investigational Site

Orange Park, Florida, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Savannah, Georgia, United States

GSK Investigational Site

Honolulu, Hawaii, United States

GSK Investigational Site

Iowa City, Iowa, United States

GSK Investigational Site

Jeffersonville, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Louisville, Kentucky, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Ann Arbor, Michigan, United States

GSK Investigational Site

Battle Creek, Michigan, United States

GSK Investigational Site

Brighton, Michigan, United States

GSK Investigational Site

Byron Center, Michigan, United States

GSK Investigational Site

Dearborn, Michigan, United States

GSK Investigational Site

Dearborn, Michigan, United States

GSK Investigational Site

Detroit, Michigan, United States

GSK Investigational Site

Flint, Michigan, United States

GSK Investigational Site

Flint, Michigan, United States

GSK Investigational Site

Flint, Michigan, United States

GSK Investigational Site

Grand Rapids, Michigan, United States

GSK Investigational Site

Grosse Point Woods, Michigan, United States

GSK Investigational Site

Lansing, Michigan, United States

GSK Investigational Site

Lansing, Michigan, United States

GSK Investigational Site

Livonia, Michigan, United States

GSK Investigational Site

Mount Clemens, Michigan, United States

GSK Investigational Site

Muskegon, Michigan, United States

GSK Investigational Site

Port Huron, Michigan, United States

GSK Investigational Site

Saginaw, Michigan, United States

GSK Investigational Site

Traverse City, Michigan, United States

GSK Investigational Site

Warren, Michigan, United States

GSK Investigational Site

Brunsville, Minnesota, United States

GSK Investigational Site

Edina, Minnesota, United States

GSK Investigational Site

Fridley, Minnesota, United States

GSK Investigational Site

Maplewood, Minnesota, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Minneapolis, Minnesota, United States

GSK Investigational Site

Saint Louis Park, Minnesota, United States

GSK Investigational Site

Saint Paul, Minnesota, United States

GSK Investigational Site

Saint Paul, Minnesota, United States

GSK Investigational Site

Woodbury, Minnesota, United States

GSK Investigational Site

New Brunswick, New Jersey, United States

GSK Investigational Site

Stony Brook, New York, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Charlotte, North Carolina, United States

GSK Investigational Site

Clinton, North Carolina, United States

GSK Investigational Site

Goldsboro, North Carolina, United States

GSK Investigational Site

Greenville, North Carolina, United States

GSK Investigational Site

Wilson, North Carolina, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Winston-Salem, North Carolina, United States

GSK Investigational Site

Canton, Ohio, United States

GSK Investigational Site

Chargrin, Ohio, United States

GSK Investigational Site

Clevand, Ohio, United States

GSK Investigational Site

Dayton, Ohio, United States

GSK Investigational Site

Dayton, Ohio, United States

GSK Investigational Site

Dayton, Ohio, United States

GSK Investigational Site

Kettering, Ohio, United States

GSK Investigational Site

Kettering, Ohio, United States

GSK Investigational Site

Lebanon, Ohio, United States

GSK Investigational Site

Mentor, Ohio, United States

GSK Investigational Site

Middletown, Ohio, United States

GSK Investigational Site

Westlake, Ohio, United States

GSK Investigational Site

Wilminton, Ohio, United States

GSK Investigational Site

Xenia, Ohio, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Portland, Oregon, United States

GSK Investigational Site

Ephrata, Pennsylvania, United States

GSK Investigational Site

Greensburg, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Philadelphia, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

Pittsburgh, Pennsylvania, United States

GSK Investigational Site

West Reading, Pennsylvania, United States

GSK Investigational Site

Lubbock, Texas, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Seattle, Washington, United States

GSK Investigational Site

Vancouver, Washington, United States

GSK Investigational Site

Vancover, Washington, United States

GSK Investigational Site

Chippewa Falls, Wisconsin, United States

GSK Investigational Site

Eau Claire, Wisconsin, United States

GSK Investigational Site

Marshfield, Wisconsin, United States

GSK Investigational Site

Minocqua, Wisconsin, United States

GSK Investigational Site

Rhinelander, Wisconsin, United States

GSK Investigational Site

Rice Lake, Wisconsin, United States

GSK Investigational Site

Stevens Point, Wisconsin, United States

GSK Investigational Site

Weston, Wisconsin, United States

GSK Investigational Site

Wisconsin Rapids, Wisconsin, United States

GSK Investigational Site

Ottawa, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Québec, Quebec, Canada

Countries

United States; Canada

Other Identifiers

NSABP FB-6

Identifier Type: OTHER

Identifier Source: secondary_id

110264

Identifier Type: -

Identifier Source: org_study_id