Sunitinib Malate or Cediranib Maleate in Treating Patients with Metastatic Soft Tissue Sarcoma

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, Treatment16 to 2011-C-0200
NCI-2013-01496, 110200, P11836, P8875_A21PAMDREVW01, 8875, NCT01391962

Trial Description



This randomized phase II trial studies how well sunitinib malate or cediranib maleate works in treating patients with soft tissue sarcoma that has spread to other parts of the body. Sunitinib malate and cediranib maleate may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. It is not yet known whether sunitinib malate or cediranib maleate is more effective in treating soft tissue sarcoma.

Further Study Information


I. Determine the objective response rate (ORR) of single agent cediranib (cediranib maleate) and single-agent sunitinib malate in patients with advanced alveolar soft part sarcoma (ASPS). (Part I)

II. Determine the ORR of cediranib in patients who progress on the sunitinib arm, and determine the ORR of sunitinib in patients who progress on the cediranib arm. (Part II)


I. Determine the progression-free survival (PFS) at 24 weeks for single-agent cediranib and single-agent sunitinib malate in patients with advanced ASPS.

II. Evaluate gene expression in tumor biopsies obtained at baseline and after treatment (at the Clinical Center, National Cancer Institute [NCI] only). (Biopsies will no longer be performed as part of this study as of 11/20/2013)

III. Perform pharmacokinetic analysis for cediranib.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: 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.

ARM II: Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

At the time of disease progression, patients in both arms cross over to the other treatment arm after a 2-week break.

After completion of study treatment, patients are followed up for 30 days.

Eligibility Criteria

Inclusion Criteria:

Patients must have histologically confirmed metastatic alveolar soft part sarcoma that is not curable by surgery; diagnosis of malignancy must be confirmed by the department of pathology at the institution where the patient is enrolled prior to patient enrollment

Patients must show evidence of objective disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) 1 on scans within the 6 month period immediately preceding enrollment; both scans used to determine disease progression should have been obtained within this 6-month period

Patients with newly diagnosed, unresectable, metastatic, and measurable ASPS who show clinical evidence of disease progression (including history and increasing physical symptoms) will also be eligible; on-study documentation will include a physician’s rationale that supports evidence of clinical disease progression (i.e., increasing tumor pain)

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

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 who have had prior monoclonal antibody therapy must have completed that therapy at least 3 half-lives of the antibody or 6 weeks ago; patients who have received more than a cumulative dose of 350 mg/m^2 of doxorubicin may be enrolled at the discretion of the coordinating center principal investigator (PI) after consultation with a cardiologist and if screening echocardiogram is normal

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 coordinating center PI’s discretion, and should have recovered to eligibility levels from any toxicities

Patients with no prior therapy are eligible, provided they have metastatic disease that is not curable by surgery

Patients age 16-17 years are eligible only if they have a body surface area (BSA) >= 1.7 m^2 or weigh >= 60 kg

Eastern Cooperative Oncology Group (ECOG) performance status =< 2

Life expectancy of greater than 3 months

Leukocytes >= 3,000/mcL

Absolute neutrophil count >= 1,500/mcL

Platelets >= 100,000/mcL

Hemoglobin >= 9 g/dL

Total serum bilirubin within normal institutional limits

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 institutional limits OR creatinine clearance >= 60 mL/min for patients with creatinine levels above institutional normal

Corrected QT interval (QTc) < 480 msec (with Bazett’s correction) in screening electrocardiogram

The following groups of patients are eligible after consultation with a cardiologist and at the coordinating center PI’s discretion, provided they have New York Heart Association class II (NYHA) cardiac function on baseline echocardiogram (ECHO)/multigated acquisition scan (MUGA):

Those with a history of class II heart failure who are asymptomatic on treatment

Those with prior anthracycline exposure greater than a cumulative dose of 350 mg/m^2

Those who have received central thoracic radiation that included the heart in the radiotherapy port

Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and 90 mmHg (diastolic) for eligibility; initiation or adjustment of BP medication is permitted prior to study entry provided that the BP reading prior to enrollment is no greater than 140/90 mmHg

Left ventricular ejection fraction (LVEF) >= institutional lower limit of normal

Strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors are not permitted within 7 days before and during the study, and strong CYP3A4 inducers are not permitted within 12 days before and during the study; every effort should be made to switch patients taking such agents or substances to other medications 1 week prior to starting therapy, particularly patients with brain metastases who are taking enzyme-inducing anticonvulsant agents; patients who require potent CYP3A4 inducers or inhibitors and cannot switch medications must have their case reviewed by the coordinating center PI and may be enrolled only after discussion with and agreement from the coordinating center PI; eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics (PK) of cediranib will be determined following review of their case by the coordinating center PI

Women of childbearing potential must have a negative pregnancy test prior to study entry; women of child-bearing potential and men must agree to use two reliable forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 2 months following study drug discontinuation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Patients who are nursing infants: breastfeeding should be discontinued if the mother is treated with the study agents

Ability to understand and the willingness to sign a written informed consent document

Patients must be able to swallow whole tablets and capsules

Exclusion Criteria:

Patients must not have received prior treatment with any vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor (e.g., cediranib, sunitinib, pazopanib, sorafenib); however, prior treatment with bevacizumab is allowed

Patients may not be receiving any other investigational agents

Major surgery within 4 weeks prior to entry into the study, or a surgical incision that is not fully healed

History of familial long QT syndrome, or use of medications that may cause QTc interval prolongation

Patients with a pre-existing thyroid abnormality who are unable to maintain thyroid function in the normal range with medication are ineligible

Warfarin and its derivatives are not allowed; patient can be receiving low molecular weight heparin if clinically indicated

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

Patients with any condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, or active peptic ulcer disease) that impairs their ability to swallow, retain, and/or absorb the drug are excluded

Patients with any of the following conditions are excluded: serious or non-healing wound, ulcer; history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of treatment; coronary/peripheral artery bypass graft or stenting within the past 12 months; or cerebrovascular accident (CVA) or transient ischemic attack within the past 12 months

Greater than 2+ proteinuria on two consecutive dipsticks taken no less than 1 week apart or 24-hour urine protein of > 1 g; patients with < 2+ proteinuria are eligible following initial determination by urinalysis within 1 week prior to enrollment and do not need the urinalysis repeated

Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
A.P. Chen, Principal Investigator

Trial Sites


Santa Monica

Sarcoma Oncology Center

Sant Prakashmir Chawla
Ph: 310-552-9999

Sant Prakashmir Chawla
Principal Investigator


Mark O Hatfield-Warren Grant Magnuson Clinical Center

A.P. Chen
Ph: 301-496-4291

A.P. Chen
Principal Investigator


Dana-Farber Cancer Institute

Suzanne George
Ph: 617-632-5204

Suzanne George
Principal Investigator


Fox Chase Cancer Center

Sujana Movva
Ph: 215-728-2814

Sujana Movva
Principal Investigator


M D Anderson Cancer Center

Shreyaskumar Rameshchandra Patel
Ph: 713-792-3626

Shreyaskumar Rameshchandra Patel
Principal Investigator



Juravinski Cancer Centre at Hamilton Health Sciences

Richard G. Tozer
Ph: 905-387-9495ext64604

Richard G. Tozer
Principal Investigator


Ontario Cancer Institute at Princess Margaret Hospital

Albiruni Ryan Abdul Razak
Ph: 419-946-4501

Albiruni Ryan Abdul Razak
Principal Investigator

Link to the current record.
NLM Identifer NCT01391962

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