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

NCT00979862 | Completed Phase 1

• 5 other identifiers: NCI-2012-02919CDR00006547150903ABTC-0903U01CA137443
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 11

Brief 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.

Conditions

Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Recurrent Adult Brain Neoplasm

Outcome Measures

Primary Outcomes (1)

• Safety profile of cediranib maleate based on the incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  The proportion of patients with serious or life threatening toxicities will be estimated along with 95% confidence intervals.

  28 days

Secondary Outcomes (4)

• Change in markers

  From baseline to up to 7 days after completion of treatment

• Overall survival (OS)

  Time from the date of treatment start to the date of death, assessed up to 6 months

• Progression-free survival

  At 6 months

• Radiographic responses using MRI scan

  Up to 6 months

Study Arms (1)

Treatment cediranib maleate, cilengitide)

EXPERIMENTAL

Part A (dose finding): Patients receive cediranib maleate PO once daily on days 1-28 and cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Part B (dose expansion): Patients are assigned to 1 of 2 groups according to prior anti-VEGF therapy (yes vs no). Patients in both groups receive cediranib maleate (administered at the safe dose determined in part A) and cilengitide as in part A.

Drug: Cediranib Maleate; Drug: Cilengitide; Other: Laboratory Biomarker Analysis

Interventions

Cediranib Maleate DRUG

Given PO

Also known as: AZD2171, AZD2171 Maleate, Recentin

Treatment cediranib maleate, cilengitide)

Cilengitide DRUG

Given IV

Also known as: EMD 121974, EMD-121974

Treatment cediranib maleate, cilengitide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment cediranib maleate, cilengitide)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Emory University/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Adult Brain Tumor Consortium

Baltimore, Maryland, 21231-1000, United States

Location

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms

Interventions

cediranib; Cilengitide

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Elizabeth Gerstner

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2009
• First Posted: September 18, 2009
• Study Start: March 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: February 1, 2014
• Last Updated: April 15, 2015

Record last verified: 2013-12

Locations

US (11)