NCT01165333

Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma

Cilengitide (EMD121974) in Combination With Irradiation in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma: Phase I Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Centre Oscar Lambret · Academic / Other
• Sex: All
• Age: 6 Months – 21 Years
• Healthy volunteers: Not accepted

Summary

The aim of the study is to determine the safety of Cilengitide in combination with radiation therapy.

Detailed description

The prognosis of children and young adults with a malignant glioma in the brain stem or a recurrent malignant glioma (in whatever site) is very poor. Over the last few decades, many therapeutic trials have been performed but have failed to significantly improve survival in these patients. There is thus a need to test new drugs in these indications. There is a strong biological rationale for the use of anti-angiogenic drugs in high-grade glioma. Cilengitide (EMD121974; Merck KgaA, Darmstadt, Germany), a cyclic pentapeptide containing the sequence RGD (cyclo-\[Arg-Gly-Asp-Dphe-(NmeVal)\]) is a selective antagonist of integrins αvβ3 and αvβ5, which are strongly involved in tumour angiogenesis. Positive results with Cilengitide in preclinical models of glioblastoma, its particularly attractive safety profile and its encouraging efficacy in phase I and II studies in adults and children make it a potentially effective molecule for the treatment of malignant glioma in children. Furthermore, its combination with radiotherapy to be appears synergistic, without any apparent increase in toxicity. In this study, Cilengitide will be evaluated when concurrently administered with radiotherapy as a first-line treatment and then as a maintenance monotherapy in children and young adults with malignant brain stem glioma. The main objective will be to determine the maximum tolerated dose (MTD) of Cilengitide when administered twice weekly as a 60-minute intra-venous infusion.

Conditions

• Diffuse Intrinsic Pontine Glioma

Interventions

Type	Name	Description
DRUG	Cilengitide dose escalation	Cilengitide will be administered intravenously over 60 minutes, twice a week, at a given dose. The Cilengitide dose (mg/m²/infusion)levels are as follows : * 240 * 480 * 720 * 1200 * 1800
DRUG	Cilengitide	Patients will be treated at the recommended dose in order to confirm the recommended cilengitide dose and to carry out the exploratory investigations
RADIATION	Concomitant radiotherapy	1.8 Gy per fraction for a total of 54 Gy over 6 weeks, from monday to friday of the first cycle. The radiation will imperatively begin between 3 and 7hours after the end of Cilengitide infusion.
BIOLOGICAL	Pharmacokinetic	A pharmacokinetic assessment for Cilengitide will be carried for all patients. The pharmacokinetic (PK) samples will be drawn during day 1 and day 2 of the first cycle of treatment.
BIOLOGICAL	Pharmacogenetic	For every patient 1 blood sample will be taken before study treatment. These blood samples can be made at any hour of the day, and does not require to be taken on an empty stomach. DNA will be extracted in the Laboratory of Pharmacology.Constitutional polymorphisms of genes will be measured before the treatment initiation.
BIOLOGICAL	Exploratory investigation	Evaluate the metabolic impact of the treatment with dynamic MRI (diffusion, perfusion, spectro), and with FDG-PETand sestamibi SPECT.

Timeline

• Start date: 2010-09-06
• Primary completion: 2014-01-01
• Completion: 2015-03-01
• First posted: 2010-07-19
• Last updated: 2026-03-16

Locations

9 sites across 1 country: France