A Phase II Study of AZD2171 in Breast Cancer Stage IV (10006202)
Condition: Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms; Breast Neoplasms, Male
Intervention: cediranib maleate; laboratory biomarker analysis
Intervention description: Given orally; Correlative studies
Intervention MeSH terms: Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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
    

Eligibility 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)