Treatment With Pazopanib for Neoadjuvant Breast Cancer

NCT00849472 | Completed Phase 2 Results

• 2 other identifiers: 110264NSABP FB-6
• Study Type: interventional
• Target: 101
• Locations: 2 countries
• Sites: 143

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.

Conditions

Neoplasms, Breast

Keywords

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

Outcome Measures

Primary Outcomes (1)

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

  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.

  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)

Secondary Outcomes (10)

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

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

• Number of Participants With Clinical Complete Response (cCR) in the Breast and Nodes at the Completion of the Doxorubicin and Cyclophosphamide (AC) Period

  From the start of the study until an average of 86.2 days (standard deviation of 5.76 days) after study entry

• Number of Participants With Clinical CR (cCR) in the Breast and Nodes at the Completion of the AC and Weekly Paclitaxel (WP) + Pazopanib Preoperative Periods

  From the start of the study until the preoperative evaluation (an average of 203.0 days [standard deviation of 23.19 days] after study entry)

• Invasive Recurrence-free Interval (IRFI)

  up to 24 months after study entry

• Number of Participants With Cardiac Toxicity (Per Common Terminology Criteria for Adverse Events Version 3) at the Completion of the AC Period

  From the start of the study until the preoperative evaluation (an average of 86.2 days [standard deviation of 5.76 days] after study entry)

Study Arms (1)

Treatment Arm

EXPERIMENTAL

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

Drug: doxorubicin + cyclophosphamide; Drug: paclitaxel + pazopanib; Procedure: surgery; Drug: pazopanib monotherapy

Interventions

doxorubicin + cyclophosphamide DRUG

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

Treatment Arm

paclitaxel + pazopanib DRUG

4 cycles of paclitaxel + pazopanib

Treatment Arm

surgery PROCEDURE

neoadjuvant surgery for breast cancer

Treatment Arm

pazopanib monotherapy DRUG

6 months of treatment with pazopanib monotherapy

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• NSABP Foundation Inc: collaborator

Study Sites (143)

GSK Investigational Site

Decatur, Alabama, 35601, United States

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GSK Investigational Site

Huntsville, Alabama, 35801, United States

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GSK Investigational Site

Huntsville, Alabama, 35805, United States

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Antioch, California, 94531, United States

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Fremont, California, 94538, United States

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Hayward, California, 94545, United States

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Oakland, California, 94611, United States

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Redwood City, California, 94063, United States

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Richmond, California, 94801, United States

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Roseville, California, 95661, United States

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Sacramento, California, 95823, United States

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GSK Investigational Site

Sacramento, California, 95825, United States

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San Francisco, California, 94115, United States

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San Jose, California, 95119-1110, United States

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San Rafael, California, 94903, United States

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Santa Clara, California, 95051, United States

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Santa Rosa, California, 95403-2192, United States

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South San Francisco, California, 94080, United States

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Stockton, California, 95210, United States

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Vacaville, California, 95688, United States

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Vallejo, California, 94589, United States

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Walnut Creek, California, 94596, United States

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Colorado Springs, Colorado, 80907, United States

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Denver, Colorado, 80205, United States

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GSK Investigational Site

Denver, Colorado, 80210, United States

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GSK Investigational Site

Denver, Colorado, 80218, United States

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GSK Investigational Site

Denver, Colorado, 80224, United States

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GSK Investigational Site

Denver, Colorado, 80244, United States

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Englewood, Colorado, 80113, United States

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Greeley, Colorado, 80631, United States

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Lafayette, Colorado, 80026, United States

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Wheat Ridge, Colorado, 80033, United States

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Wheat Ridge, Colorado, 80333, United States

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Fernandina Beach, Florida, 32034, United States

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Gainesville, Florida, 32610, United States

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Jacksonville, Florida, 32205, United States

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Jacksonville, Florida, 32207, United States

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Jacksonville, Florida, 32256, United States

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Jacksonville, Florida, 32258, United States

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Orange Park, Florida, 32073, United States

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Savannah, Georgia, 31404, United States

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GSK Investigational Site

Savannah, Georgia, 31405, United States

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Honolulu, Hawaii, 96819, United States

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Iowa City, Iowa, 52242, United States

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Jeffersonville, Kentucky, 47130, United States

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Louisville, Kentucky, 40202, United States

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Louisville, Kentucky, 40207, United States

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Louisville, Kentucky, 40217, United States

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Louisville, Kentucky, United States

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Baltimore, Maryland, 21237, United States

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Ann Arbor, Michigan, 48106, United States

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Battle Creek, Michigan, 49016, United States

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Brighton, Michigan, 48114, United States

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Byron Center, Michigan, 49519, United States

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Dearborn, Michigan, 48123, United States

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Dearborn, Michigan, 48162, United States

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Detroit, Michigan, 48236, United States

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Flint, Michigan, 48502, United States

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Flint, Michigan, 48503, United States

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Flint, Michigan, 48532, United States

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Grand Rapids, Michigan, 49503, United States

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Grosse Point Woods, Michigan, 19229, United States

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Lansing, Michigan, 48910, United States

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Lansing, Michigan, 48912, United States

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Livonia, Michigan, 48154, United States

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Mount Clemens, Michigan, 48043, United States

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Muskegon, Michigan, 49444, United States

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Port Huron, Michigan, 48060, United States

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Saginaw, Michigan, 48601, United States

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Traverse City, Michigan, 49684, United States

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Warren, Michigan, 48093, United States

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Brunsville, Minnesota, 55337, United States

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Edina, Minnesota, 55435, United States

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Fridley, Minnesota, 55432, United States

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Maplewood, Minnesota, 55109, United States

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Minneapolis, Minnesota, 55433, United States

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Minneapolis, Minnesota, 55454, United States

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Saint Louis Park, Minnesota, 55416, United States

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Saint Paul, Minnesota, 55101, United States

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Saint Paul, Minnesota, 55102, United States

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Woodbury, Minnesota, 55125, United States

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New Brunswick, New Jersey, 08901, United States

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Stony Brook, New York, 11794, United States

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Charlotte, North Carolina, 28203, United States

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Charlotte, North Carolina, 28204, United States

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GSK Investigational Site

Charlotte, North Carolina, 28210, United States

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Charlotte, North Carolina, 28211, United States

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Charlotte, North Carolina, 28262, United States

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Clinton, North Carolina, 28328, United States

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Goldsboro, North Carolina, 27534, United States

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Greenville, North Carolina, 27834, United States

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Wilson, North Carolina, 27893, United States

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Winston-Salem, North Carolina, 27014, United States

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Winston-Salem, North Carolina, 27157, United States

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Canton, Ohio, 44710, United States

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Chargrin, Ohio, 44122, United States

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Clevand, Ohio, 44106, United States

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Dayton, Ohio, 45331, United States

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Dayton, Ohio, 45415, United States

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Dayton, Ohio, 45429, United States

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Kettering, Ohio, 45409, United States

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Kettering, Ohio, 45429, United States

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Lebanon, Ohio, 45036, United States

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Mentor, Ohio, 44060, United States

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Middletown, Ohio, 45042, United States

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Westlake, Ohio, 44145, United States

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Wilminton, Ohio, 45042, United States

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Xenia, Ohio, 45385, United States

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Portland, Oregon, 97213, United States

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Portland, Oregon, 97225, United States

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Portland, Oregon, United States

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Ephrata, Pennsylvania, 17522, United States

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Greensburg, Pennsylvania, 15601, United States

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Philadelphia, Pennsylvania, 19107, United States

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Philadelphia, Pennsylvania, 19115, United States

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Philadelphia, Pennsylvania, 19141, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Pittsburgh, Pennsylvania, 15215, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Pittsburgh, Pennsylvania, 15237, United States

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West Reading, Pennsylvania, 19611, United States

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Lubbock, Texas, 79410, United States

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Richmond, Virginia, 23235, United States

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Richmond, Virginia, 23298, United States

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Seattle, Washington, 98101, United States

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Vancouver, Washington, 98668, United States

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Vancover, Washington, 98684, United States

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Chippewa Falls, Wisconsin, 54729, United States

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Eau Claire, Wisconsin, 54701, United States

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Marshfield, Wisconsin, 54449, United States

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Minocqua, Wisconsin, 54548, United States

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Rhinelander, Wisconsin, 54501, United States

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Rice Lake, Wisconsin, 54868, United States

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Stevens Point, Wisconsin, 54481, United States

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Weston, Wisconsin, 54476, United States

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Wisconsin Rapids, Wisconsin, 54494, United States

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Ottawa, Ontario, K1H 8L6, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Québec, Quebec, G1S 4L8, Canada

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MeSH Terms

Conditions

Breast Neoplasms

Interventions

AC protocol; Paclitaxel; pazopanib; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2009
• First Posted: February 23, 2009
• Study Start: July 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: April 1, 2013
• Last Updated: March 4, 2014
• Results First Posted: January 9, 2013

Record last verified: 2013-12

Locations

CA (6); US (137)