Overview

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

Status:
Completed
Trial end date:
2014-02-01
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
National Cancer Institute (NCI)
Treatments:
Cediranib
Maleic acid
Criteria
Inclusion Criteria:

- 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

Exclusion Criteria:

- 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