AZD2171 and Combination Chemotherapy in Treating Women With Locally Advanced Breast Cancer

June 18, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

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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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Neelima Denduluri, MD, National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2006

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2007

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 29, 2006

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 29, 2006

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 3, 2006

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 20, 2013

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 18, 2013

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CDR0000466185
  • NCI-06-C-0057
  • NCI-7088

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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