Cediranib Maleate and Cilengitide in Treating Patients With Progressive or Recurrent Glioblastoma

Completed · Phase 1

Conditions studied: Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma, Recurrent Adult Brain Neoplasm

In brief

This phase I trial is studying the side effects and best dose of cediranib maleate when given together with cilengitide in treating patients with progressive or recurrent glioblastoma. Cediranib maleate and cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor. Giving cediranib maleate together with cilengitide may kill more tumor cells.

Key facts

Study ID: NCT00979862
Run by: National Cancer Institute (NCI)
People needed: 47
Starts: 2010-03-01
Expected to finish: 2014-02-01
Last updated by the study team: 2015-04-15

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Patients must have histologically proven glioblastoma which is progressive or recurrent following radiation therapy and/or chemotherapy; patients with previous low grade glioma who progressed after radiotherapy and/or chemotherapy and are biopsied and found to have glioblastoma are eligible
Patients must have measurable contrast-enhancing progressive or recurrent glioblastoma by magnetic resonance imaging (MRI) imaging within two weeks of starting treatment; patient must be able to tolerate MRIs; computed tomography (CT) scans cannot be substituted for MRIs in this study
Patients must have recovered from severe toxicity of prior therapy; an interval of at least 3 months must have elapsed since the completion of the most recent course of radiation therapy while at least 3 weeks must have elapsed since the completion of a non-nitrosourea containing chemotherapy regimen and at least 6 weeks since the completion of a nitrosourea containing chemotherapy regimen
Patients must have a Karnofsky performance status >= 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
White blood cell (WBC) >= 3,000/mcL
Absolute neutrophil count >= 1,500/mcL
Platelets >= 100,000/mcL
Hemoglobin >= 8 g/dL
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) =< 3 × institutional upper limit of normal
Creatinine within normal institutional limits OR
Creatinine clearance >= 60 ml/min/1.73m\^2 for patients with creatinine levels above institutional normal
Patients must be able to provide written informed consent
Patients must have =< 2 recurrences/relapses of their tumor
Women of childbearing potential must have a negative pregnancy test prior to study entry; cediranib has been shown to terminate fetal development in the rat, as expected for a process dependent on vascular endothelial growth factor (VEGF) signaling; women of childbearing 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
Patients may not be breast-feeding a child
Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder; patients with prior malignancies must be disease-free for >= five years
Patients must have a Mini-Mental State Exam score of >= 15
Patients must not have received prior cilengitide or cediranib therapy for their glioblastoma
ARM 1 OF THE DOSE EXPANSION COHORT ONLY, the last treatment regimen the patient received must have included anti-VEGF treatment; a period of at least 28 days must have elapsed since the last bevacizumab treatment or a period of at least 21 days since the last short-acting anti-VEGF treatment, before treatment with cediranib/cilengitide can begin ARM 2 OF THE DOSE EXPANSION COHORT ONLY: patients must not have had prior anti-VEGF therapy
Patients must not be on enzyme-inducing anti-epileptic drugs (EIAED); patients may be on non-enzyme inducing anti-epileptic drugs (NEIAED) or not be taking any anti-epileptic drugs

You may not qualify if…

Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety
Patients with > 2 prior tumor recurrences/relapses
Patients receiving concurrent investigational agents; patients may not be receiving any other cancer related investigational agents
Although the following medications are not contraindicated on this study, each should be used with extreme caution due to potential nephrotoxic effects: vancomycin, amphotericin, pentamidine
Patients may not be on anti-coagulants (dalteparin, warfarin, etc)
Patients with a mean QTc > 500 msec (with Bazett's correction) in screening electrocardiogram or history of familial long QT syndrome or other significant electrocardiogram (ECG) abnormality noted within 14 days of treatment are ineligible
Greater than +1 proteinuria on two consecutive dipsticks taken no less than 7 days apart; however, if the first urinalysis shows no protein, then a repeat urinalysis is NOT required
Patients with a New York Heart Association classification of III or IV
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or cilengitide
Uncontrolled intercurrent illness including, but not limited to, hypertension (blood pressure > 140/90 mm Hg), 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
Pregnant women are excluded from this study because cediranib is a VEGF inhibitor with known abortifacient effects; breastfeeding should be discontinued if the mother is treated with cediranib
Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with cediranib
Patients on enzyme-inducing AED (EIAED) are not eligible for treatment on this protocol; patients previously treated with EIAED may be enrolled if they have been off the EIAED for 14 days or more prior to the first dose of cediranib or cilengitide
Patients whose MRI scan demonstrates intratumoral hemorrhage or peritumoral hemorrhage are not eligible for treatment if deemed significant by the treating physician
Patients must not have a known coagulopathy that increases risk of bleeding or a history of clinically significant hemorrhages in the past
Patients receiving concurrent VEGF inhibitors are prohibited from participating in this study
Patients with conditions requiring concurrent drugs or biologics with proarrhythmic potential

Where it is running

University of Alabama at Birmingham — Birmingham, Alabama, United States
Emory University/Winship Cancer Institute — Atlanta, Georgia, United States
Adult Brain Tumor Consortium — Baltimore, Maryland, United States
Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States
Dana-Farber Cancer Institute — Boston, Massachusetts, United States
Massachusetts General Hospital — Charlestown, Massachusetts, United States
Henry Ford Hospital — Detroit, Michigan, United States
Memorial Sloan-Kettering Cancer Center — New York, New York, United States
Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
Cleveland Clinic Foundation — Cleveland, Ohio, United States
University of Wisconsin Hospital and Clinics — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.