Clinical Trial: Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma

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

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

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

Detailed Summary:

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.


Sponsor: Centre Oscar Lambret

Current Primary Outcome: Determination of the Maximal Tolerated Dose of Cilengitide [ Time Frame: After 6 weeks of treatment ]

A DLT is defined below:

Hematological toxicity:

  • grade 4 neutropenia for more than 5 days
  • grade 3 or 4 neutropenia with documented infection
  • grade 3 or 4 thrombopenia for more than 5 days
  • requirement of platelet transfusion support for more than 5 days

Non-hematological toxicity:

Any grade 3 or 4 non-hematological toxicity of whatever duration with the exception of (i) nausea/vomiting without appropriate treatment, and (ii)isolated, transient fever occurring outside an episode of neutropenia), with the exclusion of toxicities related to any other well-identified cause.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Safety profile of the Cilengitide [ Time Frame: During all the study ]
    toxicities (NCI-CTCAE v4.0)
  • study of the pharmacoKinetic profile of Cilengitide [ Time Frame: Day 1 and 2 of first cycle ]
    Blood samples of 2 mL will be collected at each time point : before Cilengitide infusion, at the end of infusion, 30 mn after the end of infusion, 60 mn, 90 mn, 2 hrs, 4 hrs, 6 hrs, 24 hrs after the end of infusion
  • estimate efficacy in terms of response according to histopathology [ Time Frame: Every 3 cycles ]
    WHO criteria
  • Progression-free and overall survival [ Time Frame: During all the study ]
    6-month-PFS overall survival


Original Secondary Outcome:

  • Safety profile of the Cilengitide [ Time Frame: During all the study ]
    Safety according to NCI-CTCAE v4.0 criteria
  • PharmacoKinetics [ Time Frame: Day 1 and 2 of first cycle ]
    Blood samples of 2 mL will be collected at each time point : before Cilengitide infusion, at the end of infusion, 30 mn after the end of infusion, 60 mn, 90 mn, 2 hrs, 4 hrs, 6 hrs, 24 hrs after the end of infusion
  • Efficacity [ Time Frame: Every 3 cycles ]
    Efficacity according to WHO criteria
  • Progression-free and overall survival [ Time Frame: During all the study ]
    6-month-PFS overall survival


Information By: Centre Oscar Lambret

Dates:
Date Received: July 16, 2010
Date Started: August 2010
Date Completion:
Last Updated: February 15, 2016
Last Verified: February 2016