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

NCT01165333 | Completed Phase 1 DMC

• 2 other identifiers: CILENT-09022009-016870-33
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 9

Brief Summary

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

Conditions

Diffuse Intrinsic Pontine Glioma

Keywords

Paediatric oncology; Cilengitide; Glioma

Outcome Measures

Primary Outcomes (1)

• Determination of the Maximal Tolerated Dose of Cilengitide

  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.

  After 6 weeks of treatment

Secondary Outcomes (4)

• Safety profile of the Cilengitide

  During all the study

• study of the pharmacoKinetic profile of Cilengitide

  Day 1 and 2 of first cycle

• estimate efficacy in terms of response according to histopathology

  Every 3 cycles

• Progression-free and overall survival

  During all the study

Study Arms (2)

Dose escalation

EXPERIMENTAL

In the first part of the trial, a dose-ranging study in ca. 18-21 patients will be done. A standard dose escalation strategy will be used including 3 to 6 patients at each dose level, the first cohort of patients being treated at dose level one Interventions : Cilengitide dose escalation ; Concomitant radiotherapy ; Pharmacokinetic ; Pharmacogenetic

Drug: Cilengitide dose escalation; Radiation: Concomitant radiotherapy; Biological: Pharmacokinetic; Biological: Pharmacogenetic

Cohort extension

EXPERIMENTAL

An additional 20 patients will be treated at the recommended dose in order to confirm the recommended cilengitide dose and to carry out the exploratory investigations Interventions : Cilengitide ; Concomitant radiotherapy ; Pharmacokinetic ; Pharmacogenetic

Drug: Cilengitide; Radiation: Concomitant radiotherapy; Biological: Pharmacokinetic; Biological: Pharmacogenetic; Biological: Exploratory investigation

Interventions

Cilengitide DRUG

Patients will be treated at the recommended dose in order to confirm the recommended cilengitide dose and to carry out the exploratory investigations

Also known as: cilengitidine

Cohort extension

Concomitant radiotherapy RADIATION

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.

Cohort extension; Dose escalation

Pharmacokinetic BIOLOGICAL

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.

Cohort extension; Dose escalation

Pharmacogenetic BIOLOGICAL

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.

Cohort extension; Dose escalation

Exploratory investigation BIOLOGICAL

Evaluate the metabolic impact of the treatment with dynamic MRI (diffusion, perfusion, spectro), and with FDG-PETand sestamibi SPECT.

Cohort extension

Cilengitide dose escalation DRUG

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

Also known as: Cilengitidine

Dose escalation

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Histologically confirmed diffuse intrinsic pontine glioma
• Metastatic disease allowed
• MRI measurable disease according to the WHO criteria and for extension cohort
• Patient is able to undergo functional MRI (diffusion, perfusion, spectro)
• Patient is able to undergo FDG-PET and sestamibi SPECT
• Life expectancy \> 8 weeks after the start of study treatment.
• No prior chemotherapy for the present cancer; no treatment for any other cancer during the last 5 years.
• No prior cerebral radiation therapy
• Age \> 6 months and \< 21 years
• Lansky Play Scale \> 50 or ECOG Performance Status \< 2; NB: Children and young adults with a worse performance status due to glioma-related motor paresis can be included.
• Absolute neutrophils count \> 1.5 x 109/l, Platelets \> 100 x 109/l
• Total bilirubin \< 1,5 x ULN, AST and ALT\< 2,5 x ULN
• Serum creatinine ≤ 1,5 X ULN for age. If serum creatinine \> 1,5 ULN, creatinine clearance must be \> 70 ml/min/1.73 m² (EDTA radioisotope GFR or 24 hours urines collection)
• Normal coagulation tests : prothrombin rate (prothrombin time = PT), TCA (PTT), fibrinogen
• If anticonvulsants are currently administered, the dosing regimen must be stable within 1 week prior to the first dose of Cilengitide

You may not qualify if:

• History of coagulation disorder associated with bleeding or recurrent thrombotic events.
• Prior anti-angiogenic therapy
• Any other concomitant anti-cancer treatment not foreseen by this protocol.
• Pregnancy or breast feeding woman
• Uncontrolled intercurrent illness or active infection
• Unable for medical follow-up (geographic, social or mental reasons)

Sponsors & Collaborators

• Centre Oscar Lambret: lead

Study Sites (9)

Hôpital des Enfants, Groupe Hospitalier

Bordeaux, 33076, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

CHU, Hôpital d'Enfants de la Timone

Marseille, 13385, France

Location

Centre Hospitalier Universitaire de Nantes

Nantes, 44093, France

Location

Institut Curie

Paris, 75231, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

CHU

Toulouse, 33059, France

Location

Institut Gustave-Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Diffuse Intrinsic Pontine Glioma; Glioma

Interventions

Cilengitide; Pharmacogenomic Variants; Pharmacogenomic Testing

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena; Genetic Testing; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Officials

• Pierre LEBLOND, MD

  Centre Oscar Lambret

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2010
• First Posted: July 19, 2010
• Study Start: September 6, 2010
• Primary Completion: January 1, 2014
• Study Completion: March 1, 2015
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)