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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.

Phase 2
18 Years
Not Enrolling
Glioblastoma Multiforme

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Trial Information

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.

Angiogenesis (growth of new blood vessels) is important for tumor growth. Cilengitide (EMD
121974) inhibits two receptor proteins (proteins on cell surface), called integrins αvβ3 and
αvβ5, which appear to be important in the process of angiogenesis. Cilengitide has been
shown to inhibit angiogenesis and growth of several different experimental tumors in
animals. Some tumors themselves express integrin αvβ3 and use it as a survival factor (e.g.
glioblastoma multiforme), so cilengitide might target both endothelial cells (cells of blood
vessels) and the tumor itself triggering tumor cell apoptosis (programmed cell death).

Inclusion Criteria:

- 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

- 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. avb3
and avb5 integrins).

- Measurable disease (solid contrast-enhancing lesion ~1 cm in any dimension) evaluated
by 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 PT/PTT, which are to be within 72 hours of the first dose): *
Absolute neutrophil count ≥1500/mm 3. * Platelets ≥ 100,000/mm 3. * Creatinine ≤ 1.5
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

- No more than 8 weeks have elapsed since recurrence was detected

Exclusion Criteria:

- Prior radiation therapy >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

- Concurrent illness, including severe infection, which may jeopardize the ability of
the subject to receive the procedures outlined in this protocol with reasonable

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of 6-month Progression Free Survival

Outcome Time Frame:


Safety Issue:


Principal Investigator

David Reardon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Duke University


United States: Food and Drug Administration

Study ID:

EMD 121974-009



Start Date:

October 2004

Completion Date:

December 2007

Related Keywords:

  • Glioblastoma Multiforme
  • brain cancer
  • brain tumor
  • Brain Neoplasms
  • Glioblastoma



Memorial Sloan Kettering Cancer Center New York, New York  10021
Massachusetts General Hospital Boston, Massachusetts  02114-2617
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Duke University Medical Center Durham, North Carolina  27710
Northwestern University Chicago, Illinois  60611
Henry Ford Health System Detroit, Michigan  48202
Barrow Neurological Institute Phoenix, Arizona  85013
UCLA Medical Center Los Angeles, California  90095-7059
Indiana University Medical Center Indianapolis, Indiana  46202
Washington University St. Louis, Missouri  63110
University of Texas MD Anderson Cancer Center Houston, Texas  77030
University of Massachusetts Worcester, Massachusetts  01655
Denise Damek Aurora, Colorado  80010
Good Samaritan Hospital/Tri Health Hatton Center Cincinnati, Ohio  45206
Baylor University Medical Center at Dallas Dallas, Texas  75246
University of Vermont/Fletcher Allen Healthcare Burlington, Vermont  05401
University of Virginia Health System Charlottesville, Virginia  22903