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Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma

Phase 2
21 Years
Not Enrolling
Childhood High-grade Cerebellar Astrocytoma, Childhood High-grade Cerebral Astrocytoma, Recurrent Childhood Anaplastic Astrocytoma, Recurrent Childhood Anaplastic Oligoastrocytoma, Recurrent Childhood Anaplastic Oligodendroglioma, Recurrent Childhood Brain Tumor, Recurrent Childhood Cerebellar Astrocytoma, Recurrent Childhood Cerebral Astrocytoma, Recurrent Childhood Glioblastoma, Recurrent Childhood Visual Pathway and Hypothalamic Glioma

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Trial Information

Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma


I. To determine the objective response rate to cilengitide in younger patients with
recurrent or progressive high-grade glioma that is refractory to standard therapy.


I. To estimate the distribution of time to progression, time to treatment failure, and time
to death in these patients.

II. To estimate the rate of toxicity, especially symptomatic intratumoral hemorrhage, in
these patients.

III. To evaluate the pharmacokinetics of Cilengitide in plasma using a limited sampling

IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, BCRP, P-gp) and
relate to Cilengitide disposition.

OUTLINE: This is a multicenter study.

Patients receive cilengitide IV over 1 hour on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months for 2 years and then
periodically for 3 years.

Inclusion Criteria:

- Histologically confirmed* primary CNS high-grade glioma, including any of the

- Glioblastoma multiforme

- Anaplastic astrocytoma

- Anaplastic oligodendroglioma

- High-grade astrocytoma not otherwise specified (i.e., anaplastic ganglioglioma,
anaplastic mixed glioma, or anaplastic mixed glioneuronal tumors)

- No diffuse pontine gliomas, gliomatosis cerebri, and primary spinal cord
high-grade astrocytoma

- Gliosarcoma

- Recurrent or progressive disease that is refractory to standard therapy

- Radiographically documented measurable disease

- Lesion must be at least twice the thickness of the image from which it is
derived (e.g., 10 mm for a 5 mm slice thickness)

- No diffuse pontine gliomas

- No evidence of prior CNS bleeding

- Karnofsky performance status (PS) 50-100% (patients > 16 years of age)

- Lansky PS 50-100% (patients ≤ 16 years of age)

- Life expectancy ≥ 8 weeks

- ANC ≥ 1,000/μL

- Platelet count ≥ 100,000/μL (transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70mL/min OR serum
creatinine based on age/gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 to < 2 years of age)

- 0.8 mg/dL (2 to < 6 years of age)

- 1.0 mg/dL (6 to < 10 years of age)

- 1.2 mg/dL (10 to < 13 years of age)

- 1.5 mg/dL (male) or 1.4mg/dL (female) (13 to < 16 years of age)

- 1.7 mg/dL (male) or 1.4mg/dL (female) (≥ 16 years of age)

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

- ALT and AST ≤ 2.5 times ULN for age

- No evidence of dyspnea at rest

- No exercise intolerance

- Pulse oximetry > 94%, if determination is clinically indicated

- Seizure disorder is allowed provided it is well-controlled with anticonvulsants

- No uncontrolled infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Recovered from all prior therapy

- No more than two prior treatments for high-grade glioma (i.e., one initial treatment
and one treatment for relapse)

- More than 2 weeks since prior myelosuppressive chemotherapy (≥ 6 weeks for

- At least 1 week since prior non-myelosuppressive chemotherapy, immunotherapy, or
biologic therapy

- At least 2 weeks since prior local palliative radiotherapy (i.e., small port) to a
symptomatic non-target lesion only

- At least 3 months since prior craniospinal radiotherapy

- At least 6 weeks since prior substantial bone marrow radiotherapy

- At least 6 months since prior allogeneic stem cell transplantation (SCT) or rescue

- Patients who have undergone prior allogeneic SCT and who have graft-versus-host
disease (GVHD) must have controlled GVHD that is ≤ grade 2

- At least 1 month since prior autologous SCT

- More than 1 week since prior growth factors (> 3 weeks for pegfilgrastim [Neulasta®])

- No other concurrent anticancer therapy, including chemotherapy or immunomodulating

- No other concurrent experimental agents or therapies

- No concurrent alternative or complimentary therapies

- No concurrent homeopathic medicines

- No concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid

- No concurrent steroids as anti-emetics

- Concurrent steroids for treatment of increased intracranial pressure allowed if on a
stable or decreasing dose for ≥ 1 week before study entry

- Concurrent radiotherapy to localized painful lesions allowed provided ≥ 1 measurable
lesion is not irradiated

Type of Study:


Study Design:

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

Outcome Measure:

Objective response rate to cilengitide

Outcome Description:

Objective response is defined as defined as complete response or partial response that is sustained for at least 4 weeks, or stable disease that is sustained for at least 12 weeks while on stable or decreasing dose of corticosteroids. The study will employ a two stage rule. Objective response rate among study participants will be estimated as a simple binomial proportion. The exact 95% confidence interval for objective response rate will be calculated.

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Tobey MacDonald

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

June 2008

Completion Date:

Related Keywords:

  • Childhood High-grade Cerebellar Astrocytoma
  • Childhood High-grade Cerebral Astrocytoma
  • Recurrent Childhood Anaplastic Astrocytoma
  • Recurrent Childhood Anaplastic Oligoastrocytoma
  • Recurrent Childhood Anaplastic Oligodendroglioma
  • Recurrent Childhood Brain Tumor
  • Recurrent Childhood Cerebellar Astrocytoma
  • Recurrent Childhood Cerebral Astrocytoma
  • Recurrent Childhood Glioblastoma
  • Recurrent Childhood Visual Pathway and Hypothalamic Glioma
  • Astrocytoma
  • Brain Neoplasms
  • Glioblastoma
  • Glioma
  • Oligodendroglioma
  • Optic Nerve Glioma



Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Newark Beth Israel Medical Center Newark, New Jersey  07112
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Children's Hospital Medical Center of Akron Akron, Ohio  44308
Montefiore Medical Center Bronx, New York  10467-2490
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Wayne State University Detroit, Michigan  48202
Oregon Health and Science University Portland, Oregon  97201
Seattle Children's Hospital Seattle, Washington  98105
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Childrens Memorial Hospital Chicago, Illinois  60614
Kaiser Permanente-Oakland Oakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057
New York University Langone Medical Center New York, New York  10016
University of California San Francisco Medical Center San Francisco, California  94143
Palmetto Health Richland Columbia, South Carolina  29203
T C Thompson Children's Hospital Chattanooga, Tennessee  37403