Cediranib Maleate in Treating Patients with Metastatic Soft Tissue Sarcoma
Basic Trial Information
|Phase II||Treatment||Active||18 and over||8463|
NCI-2013-01452, P09512, 090192, 09-C-0192, NCT00942877
This phase II trial studies how well cediranib maleate works in treating patients with soft tissue sarcoma that has spread to other places in the body. Cediranib maleate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by preventing the growth of new blood vessels that tumors need to grow.
Further Study Information
I. To determine the response rate (partial response [PR] + complete response [CR]) of AZD2171 (cediranib maleate) in adult patients with alveolar soft part sarcoma (ASPS). (Adult patients)
II. To compare gene expression profiles between pre-treatment and on-treatment biopsy specimens. (Adult patients)
III. To determine if pediatric patients with ASPS will experience at least a minimal response rate when treated with AZD2171. (Pediatric patients)
I. Retrospectively compare volumetric density (total volume of viable tumor [TVVT]) (all lesions; volume/density) vs. pre-determined Response Evaluation Criteria in Solid Tumors (RECIST) (axial only).
II. Correlate TVVT, RECIST, and treatment response.
Patients receive cediranib maleate orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
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 >= 20 mm with conventional techniques or as >= 10 mm 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 >= 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 >= 4 weeks prior to study enrollment and all associated toxicities resolved to eligibility levels; patients must be >= 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 have recovered 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) >= 1.04 m^2
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 for adults, Karnofsky performance status >= 50% for pediatric patients > 10 years of age, and Lansky performance status >= 50 for pediatric patients =< 10 years of age
Life expectancy of greater than 8 weeks
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Total bilirubin < 1.5 X institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
Creatinine within normal limits based on age as follows:
Age (years): maximum serum creatinine (mg/dL)
- =< 5: 0.8 mg/dL
- 5 < age =< 10: 1.0 mg/dL
- 10 < age =< 15: 1.2 mg/dL
- > 15: 1.5 mg/dL
OR creatinine clearance >= 60 mL/min for adults or >= 60 mL/min/1.73m^2 for children with creatinine levels above institutional upper limit of normal
Corrected QT interval (QTc) must be < 500 msec
Pediatric patients: normal left ventricular function with ejection fraction > 55% or shortening fraction >= 27%
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
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
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 > 500 msec (with Bazett’s correction) in screening electrocardiogram or history of familial long QT syndrome
Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with AZD2171
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
Adult patients with hypertension not controlled by medical therapy (hypertension defined
as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg 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 =< the 95th percentile for age, height, and gender, and not be receiving medication for treatment of hypertension
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
National Cancer Institute
- National Cancer Institute
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT00942877
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.