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Adult Giant Cell GlioblastomaPhase 1NCT00979862

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

A Phase 1 study testing Cediranib Maleate, Cilengitide and Laboratory Biomarker Analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cediranib Maleate, Cilengitide and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
47 participants
Where
11 sitesUnited States
Study dates
Mar 2010to Feb 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Emory University/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Adult Brain Tumor Consortium

    Baltimore, Maryland, 21231-1000

  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Massachusetts General Hospital

    Charlestown, Massachusetts, 02129

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase Ib Study of Cediranib in Combination With Cilengitide in Patients With Recurrent Glioblastoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the safety profile of cediranib (cediranib maleate) in combination with cilengitide in patients with recurrent glioblastoma (Part A).

SECONDARY OBJECTIVES:

  1. To estimate overall survival. II. To estimate the proportion of radiographic responses in recurrent glioblastoma patients with measurable disease treated with cediranib and cilengitide.

III. To estimate the proportion of patients alive and progression free at 6 months (APF6) in patients with recurrent glioblastoma treated at the safe dose as determined in Part A (Part B).

IV. To explore potential imaging techniques and biomarkers to capture the disease process through treatment.

OUTLINE: This is a dose-escalation study of cediranib maleate. Patients are initially enrolled in the dose-finding portion of the study (part A). Once the safe dose of cediranib maleate is determined, additional patients are enrolled in the dose-expansion portion of the study (part B).

Part A (dose finding): Patients receive cediranib maleate orally (PO) once daily on days 1-28 and cilengitide intravenously (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.

After completion of study therapy, patients are followed up every 2 months.

Being tested
Cediranib Maleate, Cilengitide, Laboratory Biomarker Analysis
Medical subject headings
Glioblastoma, Gliosarcoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cediranib MaleateDrug

    Also called AZD2171, AZD2171 Maleate, Recentin

    Given PO

  • CilengitideDrug

    Also called EMD 121974, EMD-121974

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

Study groups in NCT00979862
Study groupRoleWhat they receive
Treatment cediranib maleate, cilengitide)ExperimentalPart 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.
Receives: Drug: Cediranib Maleate; Drug: Cilengitide; Other: Laboratory Biomarker Analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 28 days

Secondary outcomes (4)

  1. Change in markers

    Summarized using descriptive statistics. Statistical graphics such as box plots will be used to present the summary statistics at each time point. The differences before and during treatment will be tested using paired statistics.

    Measured: From baseline to up to 7 days after completion of treatment

  2. Overall survival (OS)

    Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method.

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

  3. Progression-free survival

    The probability of 6-month progression-free survival will be estimated using binomial distribution.

    Measured: At 6 months

  4. Radiographic responses using MRI scan

    The probability of the responses will be estimated using binomial distribution.

    Measured: Up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2009 (estimated)
  2. Study startMar 2010
  3. Primary completionMay 2012
  4. Study completionFeb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
47 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00979862
Sponsor's protocol ID
NCI-2012-02919
Other IDs
NCI-2012-02919, CDR0000654715, 0903, ABTC-0903, U01CA137443
Status last verified
Dec 2013
First submitted
17 Sep 2009
Last updated
15 Apr 2015
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cediranib Maleate, Cilengitide and Laboratory Biomarker Analysis in people with Adult Giant Cell Glioblastoma and Adult Glioblastoma, run by National Cancer Institute (NCI) at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00979862.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2015.

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