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Treatment With Pazopanib for Neoadjuvant Breast Cancer
This study is currently recruiting participants.
Verified by GlaxoSmithKline, August 2009
First Received: February 12, 2009   Last Updated: August 27, 2009   History of Changes
Sponsored by: GlaxoSmithKline
Information provided by: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00849472
  Purpose

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.


Condition Intervention Phase
Breast Cancer
Drug: pazopanib monotherapy
Procedure: surgery
Drug: doxorubicin + cyclophosphamide
Drug: paclitaxel + pazopanib
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase II Clinical Trial of Four Cycles of Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel Given Concurrently With Pazopanib as Neoadjuvant Therapy Followed by Postoperative Pazopanib for Women With Locally Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • To determine the pathologic complete response rate in the breast and axillary lymph nodes as well as any non-axillary SN (pCR breast and nodes) following completion of neoadjuvant therapy [ Time Frame: Following surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pathologic complete response rate in breast [ Time Frame: Following surgery ] [ Designated as safety issue: No ]
  • Clinical complete response rate in breast and nodes [ Time Frame: After last dose of AC, after last dose of paclitaxel before surgery ] [ Designated as safety issue: No ]
  • Invasive recurrence-free interval (IRFI) [ Time Frame: 24 months following study entry ] [ Designated as safety issue: No ]
  • Cardiac toxicity [ Time Frame: After last dose of AC, after last dose of paclitaxel, 3 and 6 months after postoperative pazopanib, 24 months after study entry. ] [ Designated as safety issue: Yes ]
  • Thyroid toxicity [ Time Frame: After completion of AC through 24 months following study entry. ] [ Designated as safety issue: Yes ]
  • Other Toxicity [ Time Frame: From first dose of AC through 24 months following study entry. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: July 2009
Estimated Study Completion Date: October 2012
Estimated Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: pazopanib monotherapy
6 months of treatment with pazopanib monotherapy
Procedure: surgery
neoadjuvant surgery for breast cancer
Drug: doxorubicin + cyclophosphamide
4 cycles of doxorubicin + cyclophosphamide followed by 4 cycles of paclitaxel + pazopanib.
Drug: paclitaxel + pazopanib
4 cycles of paclitaxel + pazopanib

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00849472

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718

Locations
United States, Alabama
GSK Investigational Site Not yet recruiting
Huntsville, Alabama, United States, 35801
GSK Investigational Site Not yet recruiting
Decatur, Alabama, United States, 35601
GSK Investigational Site Not yet recruiting
Huntsville, Alabama, United States, 35805
United States, Iowa
GSK Investigational Site Not yet recruiting
Iowa City, Iowa, United States, 52242
United States, New Jersey
GSK Investigational Site Recruiting
New Brunswick, New Jersey, United States, 08901
Canada, Quebec
GSK Investigational Site Not yet recruiting
Montreal, Quebec, Canada, H2L 4M1
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GSK ( Study Director )
Study ID Numbers: 110264, NSABP FB-6
Study First Received: February 12, 2009
Last Updated: August 27, 2009
ClinicalTrials.gov Identifier: NCT00849472     History of Changes
Health Authority: Canada: Health Canada;   United States: Food and Drug Administration;   United States: Institutional Review Board

Keywords provided by GlaxoSmithKline:
Neoadjuvant Breast Cancer
Doxorubicin
Pazopanib (GW786034)
Paclitaxel
cyclophosphamide
NSABP Foundation, Inc.

Study placed in the following topic categories:
Skin Diseases
Immunologic Factors
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Immunosuppressive Agents
Doxorubicin
Anti-Bacterial Agents
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Mitosis Modulators
Physiological Effects of Drugs
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

ClinicalTrials.gov processed this record on August 30, 2009