Phase II Study of Cediranib (AZD2171) in Patients With Alveolar Soft Part Sarcoma

• 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