Sunitinib Malate or Cediranib Maleate in Treating Patients with Metastatic Soft Tissue Sarcoma That Cannot Be Removed by Surgery
Basic Trial Information
|Phase II||Biomarker/Laboratory analysis, Treatment||Active||16 to 20||8875|
NCI-2013-01496, 110200, P11836, 11-C-0200, NCT01391962
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 and cannot be removed by surgery. 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.
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
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
- AstraZeneca Pharmaceuticals LP
- Pfizer, Inc
- National Cancer Institute
Sarcoma Oncology Center
Sant Prakashmir Chawla
Sant Prakashmir Chawla
Memorial Sloan-Kettering Cancer Center
A P Chen
A P Chen
Fox Chase Cancer Center
M D Anderson Cancer Center
Shreyaskumar Rameshchandra Patel
Shreyaskumar Rameshchandra Patel
University Health Network-Princess Margaret Hospital
Albiruni Ryan Abdul Razak
Albiruni Ryan Abdul Razak
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01391962
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.