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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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.

Detailed Summary:

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, breast cancer resistance protein [BCRP], P-glycoprotein [P-gp]) and relate to cilengitide disposition.

OUTLINE:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Objective Response to Cilengitide [ Time Frame: Up to 16 weeks ]

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.


Original Primary Outcome: Objective response

Current Secondary Outcome:

  • Time to Tumor Progression (TTP) [ Time Frame: Time from study enrollment to radiographically determined tumor progression or recurrence, assessed up to 5 years ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.


Original Secondary Outcome:

  • Time to tumor progression
  • Time to treatment failure
  • Time to death
  • Toxicity as assessed by NCI CTCAE v3.0


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 14, 2008
Date Started: June 2008
Date Completion:
Last Updated: May 5, 2014
Last Verified: October 2011