A Phase II Study of AZD2171 in Breast Cancer Stage IV (10006202)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00244881
First received: October 25, 2005
Last updated: April 30, 2014
Last verified: November 2013
  Purpose

AZD2171 (cediranib maleate) 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. This phase II trial is studying how well AZD2171 works in treating patients with refractory stage IV breast cancer


Condition Intervention Phase
Male Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: cediranib maleate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of AZD2171 in Breast Cancer Stage IV (10006202)

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Fraction of Patients With Increased Levels of Circulating Endothelial Cells [ Time Frame: After 3 weeks of treatment ] [ Designated as safety issue: No ]
    An exact 95% confidence interval (CI) will be calculated for the CEC response rate. With 26 patients, this CI will be no wider than 40% (e.g., if 13 of 26 patients respond, the CI is 30% to 70%).

  • Objective Response Rate (ORR = CR + PR) Classified According to RECIST Criteria [ Time Frame: Up to 7 years ] [ Designated as safety issue: No ]
    RECIST 1.0 Criteria


Secondary Outcome Measures:
  • Response/Stable Disease Rate Defined as the Percentage of Patients Demonstrating CR + PR + SD [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: September 2005
Study Completion Date: December 2007
Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cediranib maleate)
Patients receive oral AZD2171 once daily for 42 days. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.
Drug: cediranib maleate
Given orally
Other Names:
  • AZD2171
  • Recentin
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Evaluation of the fraction of patients with increased levels of circulating endothelial cells after 3 weeks of treatment with AZD2171.

II. Estimation of the objective response rate (ORR = CR + PR) among patients with refractory breast cancer receiving AZD2171.

SECONDARY OBJECTIVES:

I. Estimation of the response/stable disease rate (RSDR = CR + PR + SD). II. Characterization of the toxicity associated with AZD2171 in this cohort of patients.

III. Analyses to correlate serial quantification of circulating endothelial cells and circulating tumor cells with traditional clinical endpoints including RR and TTP.

IV. Develop pharmacodynamic measures of AZ2171 activity based on monocyte count and VEGFR-1 phosphorylation within monocytes.

OUTLINE: This is a nonrandomized, open-label, multicenter study.

Patients receive oral AZD2171 once daily for 42 days. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed Breast Cancer, stage IV, including:

    • "Breast neoplasms malignant and unspecified (incl nipple)","Breast and nipple neoplasms malignant","Breast cancer stage IV","10006202"
    • Breast neoplasms malignant and unspecified (incl nipple)","Breast and nipple neoplasms malignant","Breast cancer recurrent","10006198"
    • "Breast neoplasms malignant and unspecified (incl nipple)","Breast and nipple neoplasms malignant","Inflammatory carcinoma of breast stage IV","10021979"
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan
  • Patients must have refractory breast cancer, defined as overt clinical tumor progression on most recent treatment with either hormonal therapy, chemotherapy, and/or trastuzumab therapy; patients with up to 3 prior chemotherapy regimens and with any number of biological (hormonal, trastuzumab) regimens for metastatic breast cancer will be eligible
  • Life expectancy of greater than 3 months as assessed by the patient's primary oncologist
  • Absolute neutrophil count > 1,500/mcL
  • Platelets > 100,000/mcL
  • Hemoglobin >= 8 g/dL
  • Prothrombin time < institutional upper limit of normal (ULN)
  • Total bilirubin =< 1.5 x ULN
  • AST(SGOT)/ALT(SGPT) =< 2.5 × ULN
  • Creatinine within normal institutional limits
  • Urinalysis with < 1+ proteinuria
  • Troponin T or I within normal institutional limits
  • LVEF >= 45%, as assessed by echocardiogram or nuclear medicine gated study, within 30 days prior to initiating protocol-based treatment
  • At present, the potential of AZD2171 for clinically significant drug interactions involving the CYP isozymes is unknown; however, studies of the agent in rats indicated possible suppression of CYP1A that may be of biological significance; eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or PK of AZD2171 will be determined following review of their case by the Principal Investigator.
  • AZD2171 has been shown to terminate fetal development in the rat, as expected for a process dependent on VEGF signaling; for this reason, women of child-bearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • No therapeutic anti-coagulation; the use of low dose warfarin (1-2 mg/day), intermittent doses of TPA (2 mg x 1), or heparin flushes to prophylax against central venous catheter-associated clots is acceptable
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents nor have participated in an investigational trial within the past 30 days
  • Patients may not have been previously treated with an anti-angiogenesis agent
  • \Patients may not be receiving any medication that may markedly affect renal function (e.g., vancomycin, amphotericin, pentamidine); these medications will also not be permitted after the start of the study
  • Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; a head CT or MRI must be performed at baseline
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
  • Any contraindications/barrier to oral medication
  • EKG abnormalities of known clinical significance, such as prolonged QT (mean QTc > 470 msec, with Bazett's correction, in screening electrocardiogram or history of familial long QT syndrome); an EKG is required for study entry
  • Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with known abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AZD2171, breastfeeding should be discontinued if the mother is treated with AZD2171
  • HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with AZD2171; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • Patients at increased risk for compromised LVEF requiring concurrent use of drugs or biologics with proarrythmic potential; these drugs are prohibited during studies with AZD2171 (refer to Appendix J for a listing of these agents)
  • Patients with a New York Heart Association classification of III or IV are excluded (NOTE: patients classified as class II are eligible if controlled on medication and stable with increased monitoring)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244881

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Investigators
Principal Investigator: Harold Burstein Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00244881     History of Changes
Obsolete Identifiers: NCT00215488
Other Study ID Numbers: NCI-2012-02937, 05-160, U01CA062490, CDR0000445438
Study First Received: October 25, 2005
Results First Received: November 4, 2013
Last Updated: April 30, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms, Male
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cediranib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014