AZD2171 and Combination Chemotherapy in Treating Women With Locally Advanced Breast Cancer - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00310089

Purpose

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving AZD2171 together with combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed and may kill more tumor cells.

PURPOSE: This randomized clinical trial is studying how well giving AZD2171 together with combination chemotherapy works in treating women with locally advanced breast cancer.

Condition	Intervention
Breast Cancer	Biological: filgrastim Biological: pegfilgrastim Drug: cediranib maleate Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride Other: laboratory biomarker analysis Procedure: conventional surgery Procedure: neoadjuvant therapy

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Myocet Docetaxel Filgrastim Pegfilgrastim Cediranib

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Pilot Study to Evaluate The Effects of Neoadjuvant AZD2171, a VEGF Receptor Tyrosine Kinase Inhibitor With Docetaxel, Doxorubicin, and Cyclophosphamide Chemotherapy in Previously Untreated Locally Advanced Breast Cancer

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:	33
Study Start Date:	January 2006

Detailed Description:

OBJECTIVES:

Primary

Determine the overall pathologic complete response rate in women with previously untreated, locally advanced breast cancer treated with neoadjuvant AZD2171, doxorubicin hydrochloride, cyclophosphamide, and docetaxel.

Secondary

Compare changes in pretreatment levels of pKDR after 1 course of AZD2171 vs no medication.
Determine the number of patients who respond to combination therapy beginning with the second course of therapy.
Determine the clinical response rate in patients treated with this regimen.
Determine the safety of this regimen in these patients.
Determine the changes in tumor proliferation (Ki67) in these patients.
Determine the pharmacokinetics and pharmacogenetics of this regimen in these patients.
Correlate angiogenic parameters with tumor response in these patients.
Determine tumor vascularity and permeability before and after treatment as seen on dynamic contrast-enhanced MRI and initial area under the gadolinium curve.
Determine tumor choline levels before and after treatment as measured by quantitative single-voxel MR spectroscopy and correlate with response.

OUTLINE: This is a multicenter, randomized, pilot study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral AZD2171 once daily on days 1-7* during course 1. During the second and subsequent courses, patients receive oral AZD2171 once daily on days 1-21, doxorubicin hydrochloride IV over 3-5 minutes, cyclophosphamide IV over 30 minutes, and docetaxel IV over 1 hour on day 1.

Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 2-11 or pegfilgrastim SC on day 2. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: *If biopsy cannot be scheduled prior to day 7 or 8 of course 1, AZD2171 alone can be continued for up to 14 days.

Arm II (control): Beginning during the second course, patients receive AZD2171, doxorubicin hydrochloride, cyclophosphamide, docetaxel, and G-CSF or pegfilgrastim as in arm I. All patients undergo tumor biopsiesat at baseline, before courses 2 and 4, and 3 weels after completion of study treatment. Tissue is examined for various biomarkers (phosphorylated-KDR, -MAPK, and -Akt, Ki67, VEGF, and p53) and for DNA ploidy analysis**.

NOTE: **Patients also undergo dynamic contrast-enhanced MRI and quantitative magnetic resonance spectroscopy 1 week before beginning therapy, 24 hours after starting therapy, prior to courses 2, 4, and 6, and 3 weeks after completion of study treatment.

After completion of AZD2171 and chemotherapy, patients undergo surgical resection.

After completion of study treatment, patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed breast cancer, meeting 1 of the following criteria:
- Previously untreated disease
- Inflammatory disease
- Locally advanced breast cancer (stage IIIA, IIIB, or IIIC disease)
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion (longest diameter) ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan or breast MRI
Accessible tumor tissue for serial biopsy
No overexpression of HER2
No known brain metastases secondary to breast cancer
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Karnofsky performance status 60-100%
Life expectancy > 3 months
Female only
Menopausal status not specified
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin ≥ 8 g/dL
Bilirubin normal (≤ 2 times upper limit of normal [ULN] if evidence of Gilbert's disease and elevated bilirubin not related to tumor or other liver disease)
AST and ALT ≤ 2.5 ULN
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Proteinurea ≤ +1 on 2 consecutive dipsticks at least 1 week apart
INR ≤ 1.5
LVEF ≥ 50% by MUGA or echocardiogram without clinical symptoms or signs of heart failure
Fertile patients must use effective contraception
Not pregnant or nursing
Negative pregnancy test
No peripheral neuropathy ≥ grade 2
No known CNS disease, including history of stroke or seizures not controlled by standard medical therapy
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel, doxorubicin hydrochloride, or cyclophosphamide
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Hypertension
- Ongoing or active infection requiring IV antibiotics
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Peripheral vascular disease ≥ grade II
- Psychiatric illness/social situation that would preclude study treatment
No nonhealing wounds or bone fractures within the past 28 days
No history of an active malignancy except carcinoma in situ of the cervix or nonmelanomatous skin cancer in the past 5 years

PRIOR CONCURRENT THERAPY:

No prior surgery, chemotherapy, or hormonal therapy for breast cancer
No concurrent medication that may affect renal function (e.g., amphotericin B or pentamidine)
No full-dose oral or parenteral anticoagulants or chronic daily treatment with aspirin (dose > 325 mg/day) within the past 10 days
No other concurrent investigational agents
No other concurrent commercially available drugs for this cancer
No concurrent antiretroviral therapy for known HIV infection
No major surgery within the past 28 days

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00310089

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182
United States, New Jersey
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Neelima Denduluri, MD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000466185, NCI-06-C-0057, NCI-7088
Study First Received:	March 29, 2006
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00310089 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):

stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
inflammatory breast cancer

Study placed in the following topic categories:

Skin Diseases
Immunologic Factors
Breast Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Doxorubicin
Docetaxel

Anti-Bacterial Agents
Inflammatory Breast Cancer
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Cyclophosphamide
Antibiotics, Antineoplastic
Immunosuppressive Agents
Doxorubicin

Pharmacologic Actions
Docetaxel
Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

ClinicalTrials.gov processed this record on May 07, 2009