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Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy

This study has suspended participant recruitment.
(Temporarily closed to accrual.)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00679354
First received: May 14, 2008
Last updated: January 14, 2013
Last verified: November 2012
History of Changes
  Purpose

This phase II trial is studying how well cilengitide works in treating younger patients with recurrent or progressive high-grade glioma that has not responded to standard therapy. Cilengitide may stop the growth of tumor cells by blocking blood flow to the tumor


Condition Intervention Phase
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
 Drug: cilengitide
Other: laboratory biomarker analysis
Other: pharmacological study
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cilengitide (EMD 121974) (IND# 59073) in Recurrent or Progressive and Refractory Childhood High-Grade Glioma

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective response rate to cilengitide [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Time to tumor progression (TTP) [ Time Frame: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distributions of TTP will be analyzed separately using PL estimate.

  • Time to treatment failure (TTF) [ Time Frame: Time from study enrollment to tumor progression, tumor recurrence, death from any cause, or occurrence of a second malignant neoplasm, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distributions of TTF will be analyzed separately using PL estimate.

  • Time to death (TTD) [ Time Frame: Time from study enrollment to death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    The distribution of TTD will be analyzed separately using PL estimate.

  • Rate of toxicity, especially that of symptomatic intratumoral hemorrhage (ITH) assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: During each course and after completion of treatment ] [ Designated as safety issue: Yes ]
    Rates of individual toxicities including that of symptomatic ITH will be summarized in each course of treatment using standard descriptive statistical methods.

  • Pharmacokinetics of cilengitide in plasma [ Time Frame: At baseline and 1, 3, and 6 hours after the first dose of cilengitide ] [ Designated as safety issue: No ]
    Cilengitide plasma concentration-time data will be fit to a compartmental pharmacokinetic model using MAP-Bayesian estimation as implemented in ADAPT II. Individual pharmacokinetic parameters estimated will include volume of the central compartment (Vc), elimination rate constant (Ke), and half-life (t1/2). Systemic clearance (Cl) will be calculated using standard equations and AUC0-o∞ will be calculated using the log-linear trapezoidal method.

  • Pharmacogenetic polymorphisms in drug transporters and relate to cilengitide disposition [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Cilengitide systemic exposure as measured by area under the curve (AUC) and systemic clearance as the pharmacologic variable in this genotype-phenotype analysis will be used.


Estimated Enrollment: 24
Study Start Date: June 2008
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
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.
 Drug: cilengitide
Given IV
Other Name: EMD 121974
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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 strategy.

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

    • 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 nitrosoureas)
  • 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 agents
  • 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 (aspirin)
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00679354

  Show 20 Study Locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Tobey MacDonald Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00679354     History of Changes
Obsolete Identifiers: NCT01648400
Other Study ID Numbers: NCI-2009-00339, ACNS0621, U10CA098543, CDR0000595623
Study First Received: May 14, 2008
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Brain Neoplasms
Glioblastoma
Glioma
Oligodendroglioma
Optic Nerve 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
Optic Nerve Neoplasms
Cranial Nerve Neoplasms
Peripheral Nervous System Neoplasms
Cranial Nerve Diseases
Optic Nerve Diseases
Eye Diseases

ClinicalTrials.gov processed this record on May 23, 2013