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Glioblastoma MultiformePhase 2NCT00093964

Cilengitide (EMD 121974) for Recurrent Glioblastoma Multiforme (Brain Tumor)

A Phase 2 study testing Cilengitide 500 mg and Cilengitide 2000 mg in people with Glioblastoma Multiforme, run by EMD Serono at 17 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 study will investigate clinical activity, safety, and tolerability of the anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of glioblastoma multiforme (GBM). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioblastoma Multiforme
What is being tested?
Cilengitide 500 mg and Cilengitide 2000 mg
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
17 sitesUnited States
Study dates
13 Oct 2004to 21 Oct 2010
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Written informed consent obtained before undergoing any study-related activities.
  • Males or females 18 years of age or older who can be treated in an outpatient setting.
  • Histologically proven GBM, which is recurrent or progressive following surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy (Gliadel wafer therapy is not considered systemic chemotherapy). Malignancy is to be documented with a previous histopathological report.
  • Subjects initially diagnosed with other conditions similar to GBM (such as anaplastic astrocytoma [AA] or low grade glioma) that subsequently progressed to histologically proven GBM and have had surgery or biopsy, external beam radiation therapy, and 1 previous regimen of systemic chemotherapy for the original diagnosis are eligible if they meet all inclusion criteria.
  • GBM recurring only in the contralateral hemisphere must be histologically confirmed by biopsy. GBM recurring bilaterally does not need to be histologically confirmed by biopsy (i.e., if recurrence is ipsilateral and contralateral).
  • Archived tumor tissue specimens from the GBM surgery or biopsy must be available for central pathology review and exploratory analysis of angiogenic markers (e.g. αvβ3 and αvβ5 integrins).
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  • Measurable disease (solid contrast-enhancing lesion greater than or equal to (>=)1 cm in any dimension) evaluated by gadolinium-enhanced magnetic resonance imaging (Gd MRI) within 2 weeks prior to the first dose of EMD 121974.
  • At least 12 weeks have elapsed since the last radiation treatment, and at least 4 weeks have elapsed since the last chemotherapy dose (at least 6 weeks for nitrosourea-containing chemotherapy) prior to the first dose of EMD 121974.
  • If the subject underwent recent surgery, status must be >=2 weeks post surgery or >=1 week post biopsy, in stable condition, and maintained on a stable corticosteroid regimen for >=5 days prior to first dose of EMD 121974.
  • Karnofsky Performance Score (KPS) of >=70%.
  • Subjects with the potential for pregnancy or impregnating their partner must agree to follow acceptable methods of birth control to avoid conception during the study and for at least 6 months after receiving the last dose of study drug.
  • Women of childbearing potential must have a negative pregnancy test at screening.
  • Laboratory values (within 1 week prior to the first dose of EMD 121974, except for blood count and Prothrombin time (PT)/Partial thromboplastin time (PTT), which are to be within 72 hours of the first dose): Absolute neutrophil count >=1500/millimeter (mm)^3. Platelets >=100,000/mm^3. Creatinine less than or equal to (<=) 1.5 milligram/deciliter (mg/dL) or creatinine clearance >=60 mL/min. Hematocrit >=30%. Prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits. Hemoglobin >=10 mg/dL. Total bilirubin <=1.5 times the upper limit of normal. Aspartate aminotransferase and alanine aminotransferase <=2.5 times above upper limit of normal.
  • No more than 8 weeks have elapsed since recurrence was detected

Who cannot join

  • Prior radiation therapy greater than (>) 66 Gray.
  • Subject anticipates undergoing elective surgery, dental extraction, or invasive dental procedures.
  • History of recent peptic ulcer disease (endoscopically proven gastric ulcer, duodenal ulcer, or esophageal ulcer) within 6 months of enrollment.
  • History of prior malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for ≥5 years are eligible for this study.
  • History of coagulation disorder associated with bleeding or recurrent thrombotic events.
  • Concurrent illness, including severe infection, which may jeopardize the ability of the subject to receive the procedures outlined in this protocol with reasonable safety.
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  • Subject is pregnant, anticipates becoming pregnant within 6 months after study participation, or is currently breast-feeding.
  • Receiving concurrent investigational agents or has received an investigational agent within the past 30 days prior to the first dose of EMD 121974.
  • Prior antiangiogenic therapy.
  • Placement of Gliadel wafer at surgery for recurrence.
  • Unable to undergo Gd MRI.
  • Current known alcohol dependence or drug abuse.
  • Requiring concomitant chemotherapy.
  • Treatment with a prohibited concomitant medication.
  • Known hypersensitivity to the study treatment.
  • Legal incapacity or limited legal capacity.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites
  • Denise Damek

    Aurora, Colorado, 80010

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3280

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Vermont/Fletcher Allen Healthcare

    Burlington, Vermont, 05401

  • University of Virginia Health System

    Charlottesville, Virginia, 22903

  • Northwestern University

    Chicago, Illinois, 60611

  • Good Samaritan Hospital/Tri Health Hatton Center

    Cincinnati, Ohio, 45206

  • Baylor University Medical Center at Dallas

    Dallas, Texas, 75246

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • UCLA Medical Center

    Los Angeles, California, 90095

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

  • Barrow Neurological Institute

    Phoenix, Arizona, 85013

  • Washington University

    St Louis, Missouri, 63110

  • University of Massachusetts

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

Official title: A Multicenter, Open-label, Randomized, Uncontrolled, Phase IIa Trial in Subjects With Recurrent Glioblastoma Multiforme to Investigate the Clinical Activity, Safety, and Tolerability of Cilengitide (EMD 121,974) Administered as a Single Agent.

This study will investigate clinical activity, safety, and tolerability of the anti-angiogenic compound cilengitide (EMD 121974) in the treatment of first recurrence of glioblastoma multiforme (GBM).

Being tested
Cilengitide 500 mg, Cilengitide 2000 mg
Keywords
Brain cancer, Brain tumor
Medical subject headings
Glioblastoma, Brain Neoplasms

What participants receive

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

  • Cilengitide 500 mgDrug

    Also called EMD 121974

    Subjects will receive 1-hour intravenous infusion of 500 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

  • Cilengitide 2000 mgDrug

    Also called EMD 121974

    Subjects will receive 1-hour intravenous infusion of 2000 mg cilengitide twice weekly on Day 1 and 4 of each week during every 4-week cycle, for a total of 8 infusions per cycle. Cycles were repeated without pause until progressive disease (PD), unacceptable adverse events (AEs), or withdrawal of consent.

Study groups in NCT00093964
Study groupRoleWhat they receive
Cilengitide 500 Milligram (mg)ExperimentalNot described
Receives: Drug: Cilengitide 500 mg
Cilengitide 2000 mgExperimentalNot described
Receives: Drug: Cilengitide 2000 mg

What is being measured

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

  1. Percentage of Subjects With Progression-free Survival

    Progression-free survival was defined as subjects who survived greater than or equal to (>=) 180 days without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.

    Measured: Month 6

Secondary outcomes (14)
  1. Percentage of Subjects With Overall Response Rate

    Overall response rate was defined as percentage of subjects who had best response during the study which was either complete response (CR: disappearance of all tumors, no new lesions and stable or improved neurological examination) or partial response (PR: >= reduction in the sum of the products of the largest perpendicular diameters compared to the baseline sum, no worsening of evaluable lesion and stable or improved neurological examination). CR or PR was confirmed within 31 days with a repeat neuroimaging.

    Measured: From the start of treatment up to 6 years

  2. Time to Disease Progression

    Time to disease progression was defined as the number of days between the first dose and the date of first assessment of progressive disease during the study or until death. Surviving subjects without progressive disease were censored at the time of the last visit and the subject was known to be non-progressing. Disease progression was assessed as per independent central blinded radiology assessment.

    Measured: From the start of treatment until disease progression (assessed up to a maximum of 6 years)

  3. Overall Survival Time

    Survival time was defined as the number of months between the date of randomization and the date of death or the last date the subject was known to be alive.

    Measured: From the start of treatment until death (assessed up to a maximum of 6 years)

  4. Percentage of Subjects With 1-year of Survival Rate

    1-year survival rate was defined as percentage of subjects who survived for >=365 days with or without disease progression. Disease progression was assessed as per independent central blinded radiology assessment.

    Measured: From the start of treatment up to 1 year

  5. Maximum Observed Plasma Concentration (Cmax)

    Cmax is the maximum observed plasma concentration of cilengitide after administration.

    Measured: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2

  6. Time to Reach Maximum Plasma Concentration (Tmax)

    Tmax is the time to reach the maximum plasma concentration (Cmax) of cilengitide.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  7. Area Under the Plasma Concentration-time Curve From Time Zero to Infinity After Administration (AUC 0-infinity)

    AUC 0-infinity is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration of cilengitide.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  8. Apparent Terminal Rate Constant (Lambda z)

    Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression on terminal data points of the curve.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  9. Terminal Half-life (t1/2)

    The t1/2 is the time taken to eliminate half the amount of cilengitide.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  10. Mean Residence Time of Drug in the Body (MRT)

    MRT is defined as the mean duration of time a drug molecule is present in the systemic circulation.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  11. Total Body Clearance (CL) of Drug From Plasma/Cerebro Spinal Fluid (CSF)

    CL is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose divided by AUC0-infinity.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  12. Apparent Volume of Distribution During the Terminal Phase (Vz)

    Vz was calculated as Dose/(AUC0-infinity multiplied by elimination rate constant [lambda z]) following single dose.

    Measured: Pre-dose,1,1.5,2,3,4,8 and 24 hours post-infusion on Day 1 of Week 1 in Cycles 1 and 2

  13. Apparent Volume of Distribution at Steady State (Vss)

    Vss is the theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it is in blood plasma at steady state.

    Measured: Pre-dose, 1, 1.5, 2, 3, 4, 8, 24 hours post-infusion on Day 1 of Week 1 in Cycle 1 and 2

  14. Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    An AE was any untoward medical occurrence in a subject which did not necessarily have a causal relationship with the study drug. A TEAE was any AE that started on or any time after the day of first dose of cilengitide during the treatment phase or within the safety follow-up after last dose of cilengitide. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly.

    Measured: From the start of treatment up to 6 years

Timeline

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

  1. First posted11 Oct 2004 (estimated)
  2. Study start13 Oct 2004
  3. Primary completion28 Oct 2005
  4. Study completion21 Oct 2010

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00093964
Sponsor's protocol ID
EMD 121974-009
Status last verified
Jan 2019
First submitted
7 Oct 2004
Last updated
16 Apr 2019
Data monitoring committee
No

Publications

  • Reardon DA, Fink KL, Mikkelsen T, Cloughesy TF, O'Neill A, Plotkin S, Glantz M, Ravin P, Raizer JJ, Rich KM, Schiff D, Shapiro WR, Burdette-Radoux S, Dropcho EJ, Wittemer SM, Nippgen J, Picard M, Nabors LB. Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol. 2008 Dec 1;26(34):5610-7. doi: 10.1200/JCO.2008.16.7510. Epub 2008 Nov 3.

    PubMed 18981465

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cilengitide 500 mg and Cilengitide 2000 mg in people with Glioblastoma Multiforme, run by EMD Serono at 17 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 14 inclusion and 16 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 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Subjects With Progression-free Survival (time frame: Month 6). 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 NCT00093964, which also lists 1 linked publication.

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 16 Apr 2019.

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