Cilengitide in Treating Younger Patients With Recurrent or Progressive High-Grade Glioma That Has Not Responded to Standard Therapy
This phase II trial studies 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.
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
Other: laboratory biomarker analysis
Other: pharmacological study
|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|
- Objective Response to Cilengitide [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: No ]Objective response is defined as a complete response or partial response at 4 weeks that is sustained for at least another 4 weeks, or a stable disease at 4 weeks that is sustained for at least 12 weeks while on stable or decreasing dose of corticosteroids, except when corticosteroids are being used to control hydrocephaly unrelated to tumor progression.
- 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 product limit (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: Up to 5 years ] [ 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, Including of the Central Compartment (Vc), Elimination Rate Constant (Ke), and Half-life (t1/2), and Systemic Clearance (Cl) [ 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. Cl will be calculated using standard equations and area under the curve (AUC)0-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 AUC and systemic clearance as the pharmacologic variable in this genotype-phenotype analysis will be used.
|Study Start Date:||June 2008|
|Study Completion Date:||October 2012|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cilengitide)
Patients receive cilengitide IV over 1 hour (1800 mg/m2/dose, maximum 75mg/kg) 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.
Other Name: EMD 121974Other: laboratory biomarker analysis
Correlative studiesOther: pharmacological study
Other Name: pharmacological studies
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 strategy.
IV. To evaluate the pharmacogenetic polymorphisms in drug transporters (eg, breast cancer resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.
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 treatment, patients are followed up every 3 months for 2 years and then periodically for 3 years.