Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma
Condition: Sarcoma, Alveolar Soft Part
MeSH terms: Sarcoma; Sarcoma, Alveolar Soft Part
Intervention: AZD2171
Intervention description: Cediranib (AZD2171), a vascular endothelial growth factor (VEGF)/KIT tyrosine kinase inhibitor, has demonstrated antitumor activity in early phase clinical trials in adult and pediatric patients with Alveolar Soft Part Sarcoma (ASPS).
Intervention MeSH terms: Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 53.0
Sex: All
Maximum age: 16 Years
Healthy volunteers: No
Keywords: VEGF; Antiangiogenesis; Tyrosine Kinase Inhibitor; Advanced Cancer; Alveolar Soft Part Sarcoma; Sarcoma

Summary:

      Background:

        -  Alveolar soft part sarcoma is a type of cancer that develops in tissues that connect,
           support, or surround other organs in the body. It relies heavily on new blood vessels to
           grow and spread through the body. There is no effective systemic treatment for patients
           with alveolar soft part sarcoma.

        -  The drug AZD2171 (cediranib) is an experimental drug, not yet approved by the Food and
           Drug Administration. The drug blocks the creation of new blood vessels. The drug has had
           initial clinical trials, and researchers are interested in determining whether cediranib
           is effective in inhibiting tumor growth in individuals who have alveolar soft part
           sarcoma.

      Objectives:

      - To find out whether AZD2171 works in patients who have alveolar soft part sarcoma.

      Eligibility:

      - Individuals 18 years of age and older who have been diagnosed with alveolar soft part
      sarcoma.

      Design:

        -  After an initial screening visit, patients will take AZD2171 by mouth once a day, every
           day for the duration of the study. The treatment will be given in 28-day cycles.

        -  Patients will keep a study diary to record the doses taken, any missed doses, and any
           side effects.

        -  Patients will have the following tests and procedures during the treatment period:
           clinic visit with physical examination every 2 weeks during cycles 1 and 2, then at the
           start of each subsequent cycle, regular blood pressure monitoring, blood and urine
           tests, heart function tests, imagining scans to evaluate tumor size and response to the
           treatment, and possible tumor biopsy.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        Patients must have histologically confirmed alveolar soft part sarcoma. Pathology should be
        confirmed at the Laboratory of Pathology, National Institutes of Health.

        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 greater
        than or equal to 20 millimeters with conventional techniques or as greater than or equal to
        10 millimeters with spiral computed tomography (CT) scan.

        Patients must have metastatic alveolar soft part sarcoma that is not curable by surgery.
        Patients who have surgically resectable tumors with metastasis will be considered on a case
        by- case basis.

        Any prior therapy must have been completed greater than or equal to 4 weeks prior to
        enrollment on protocol and the participant must have recovered to eligibility levels from
        prior toxicity. Patients should be at least 6 weeks out from nitrosoureas and mitomycin C.
        Prior radiation should have been completed greater than or equal to 4 weeks prior to study
        enrollment and all associated toxicities resolved to eligibility levels. Patients must be
        greater than or equal to 2 weeks since any investigational agent administered as part of a
        Phase 0 study (also referred to as an early Phase I study or pre-Phase I study where a
        sub-therapeutic dose of drug is administered) at the principal investigator's (PI's)
        discretion, and should haverecovered to eligibility levels from any toxicities.

        Any degree of prior treatment is allowed, including other anti-angiogenic treatments (e.g.,
        vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors or bevacizumab). Patients
        with no prior therapy are eligible, provided they have metastatic disease that is not
        curable by surgery.

        Body surface area (BSA) greater than or equal to 1.04 square meter.

        Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 for
        adults, Karnofsky performance status greater than or equal to 50% for pediatric patients
        greater than 10 years of age, and Lansky performance status greater than or equal to 50 for
        pediatric patients less than or equal to 10 years of age.

        Life expectancy of greater than 8 weeks.

        Patients must have normal organ and marrow function as defined below:

          -  absolute neutrophil count greater than or equal to 1,500/microliter

          -  platelets greater than or equal to 100,000/microliter

          -  total bilirubin less than 1.5 times institutional upper limit of normal

          -  Aspartate aminotransferase (AST)(Serum glutamic Oxaloacetic transaminase
             (SGOT)/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase (SGPT))
             less than or equal to 2.5 times institutional upper limit of normal

          -  creatinine within normal limits based on age as follows:

        Age (Years) Maximum Serum Creatinine (milligrams per deciliter)

        less than or equal to 5 0.8

        5 less than age less than or equal to 10 1.0

        10 less than age less than or equal to 15 1.2

        greater than 15 1.5

        OR

        creatinine clearance greater than or equal to 60 milliliter/min for adults or greater than
        or equal to 60 milliliter/min/1.73m^2 for children with creatinine levels above
        institutional upper limit of normal.

        Corrected QT interval (QTc) must be less than 500 msec.

        Pediatric patients: Normal left ventricular function with ejection fraction greater than
        55% or shortening fraction greater than or equal to 27%.

        At present, the potential of Cediranib (AZD2171) for clinically significant drug
        interactions involving the cytochrome P450 (CYP) isozymes is unknown. However, studies of
        the agent in rats indicated possible suppression of cytochrome P450, family 1, subfamily A
        (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 of
        pharmacokinetics (PK) of AZD2171 will be determined following review of their case by the
        Principal Investigator. Efforts should be made to switch patients with brain metastases who
        are taking enzyme-inducing anticonvulsant agents to other medications one week prior to
        starting therapy.

        AZD2171 has been shown to terminate fetal development in the rat, as expected for a process
        dependent on vascular endothelial growth factor (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.

        Ability to understand and the willingness to sign a written informed consent document.

        Patients should not be receiving any other investigational agents.

        Prior therapy with anti-angiogenic agents is permitted.

        EXCLUSION CRITERIA:

        Patients with clinically significant illnesses which would compromise participation in the
        study, including, but not limited to: active or uncontrolled infection, uncontrolled
        diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina
        pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia;
        or psychiatric illness/social situations that would limit compliance with study
        requirements.

        Patients may not be receiving any medication that may markedly affect renal function (e.g.,
        vancomycin, amphotericin, ibuprofen, pentamidine).

        Patients who are unable to swallow tablets.

        Mean QTc greater than 500 msec (with Bazett's correction) in screening electrocardiogram or
        history of familial long Q wave, T wave (QT) syndrome.

        Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart.

        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.

        Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
        are ineligible because of the potential for PK interactions with AZD2171.

        Adult patients with hypertension not controlled by medical therapy (hypertension defined as
        systolic blood pressure greater than 150 millimeters of mercury or diastolic pressure
        greater than 90 millimeters of mercury despite optimal medical management). Pediatric
        patients must have blood pressure (BP) within normal limits (WNL) for age. NOTE: blood
        pressure within the upper limit of normal is defined as: blood pressure less than or equal
        to the 95th percentile for age, height, and gender, and measured, and not be receiving
        medication for treatment of hypertension.