| Eligibility |
- 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.
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