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Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma (CILENT-0902)

This study is currently recruiting participants.
Verified June 2012 by Centre Oscar Lambret
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01165333
First received: July 16, 2010
Last updated: June 4, 2012
Last verified: June 2012
History of Changes
  Purpose

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


Condition Intervention Phase
Diffuse Intrinsic Pontine Glioma
 Drug: Cilengitide dose escalation
Drug: Cilengitide
Radiation: Concomitant radiotherapy
Biological: Pharmacokinetic
Biological: Pharmacogenetic
Biological: Exploratory investigation
 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cilengitide (EMD121974) in Combination With Irradiation in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma: Phase I Study

Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • Determination of the Maximal Tolerated Dose of Cilengitide [ Time Frame: After 6 weeks of treatment ] [ Designated as safety issue: Yes ]

    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.



Secondary Outcome Measures:
  • Safety profile of the Cilengitide [ Time Frame: During all the study ] [ Designated as safety issue: Yes ]
    toxicities (NCI-CTCAE v4.0)

  • study of the pharmacoKinetic profile of Cilengitide [ Time Frame: Day 1 and 2 of first cycle ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    WHO criteria

  • Progression-free and overall survival [ Time Frame: During all the study ] [ Designated as safety issue: No ]
    6-month-PFS overall survival


Estimated Enrollment: 40
Study Start Date: August 2010
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose escalation
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
 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
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.
Experimental: Cohort extension
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
 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.

  Eligibility

Ages Eligible for Study:   6 Months to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • No current organ toxicity > grade 2 according to the NCICTCAE version 4.0, especially cardiovascular or renal disease (nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment). In case of known or possible cardiac disease, a cardiological advice will be required prior to the inclusion in the study
  • If anticonvulsants are currently administered, the dosing regimen must be stable within 1 week prior to the first dose of Cilengitide
  • If corticosteroids are administered, the dosing regimen must be stable ≥ 5 days prior to the first dose of Cilengitide.
  • Effective contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the last administration of Cilengitide.
  • Negative pregnancy test (serum beta-HCG) within 1 week prior to start of study treatment in females of reproductive potential
  • Patient covered by government health insurance
  • Written informed consent given by patient and/or parents/ guardians prior to the study participation

Exclusion Criteria:

  • Inclusion criteria failure
  • 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.
  • Concomitant inclusion in another therapeutic clinical trial; participation in another therapeutic clinical trial during the last 30 days.
  • Pregnancy or breast feeding woman
  • Uncontrolled intercurrent illness or active infection
  • Unable for medical follow-up (geographic, social or mental reasons)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01165333

Contacts
Contact: Pierre LEBLOND, MD (33)3 20 29 59 56 p-leblond@o-lambret.fr
Contact: Yvette VENDEL, Sponsor CRA (33)3 20 29 59 40 y-vendel@o-lambret.fr

Locations
France
Hôpital des Enfants, Groupe Hospitalier Recruiting
Bordeaux, France, 33076
Contact: Yves PEREL, PhD     (33)557820438     yves.perel@chu-bordeaux.fr    
Sub-Investigator: Céline de BOUYN-ICHER, MD            
Sub-Investigator: Charlotte JUBERT, MD            
Sub-Investigator: Aymeri HUCHET, MD            
Centre Oscar Lambret Recruiting
Lille, France, 59020
Contact: Pierre LEBLOND, MD     (33)320295956     p-leblond@o-lambret.fr    
Contact: Yvette VENDEL, sponsor CRA            
Sub-Investigator: A-Sophie DEFACHELLES, MD            
Sub-Investigator: Bernard COCHE-DEQUEANT, MD            
Principal Investigator: Pierre LEBLOND, MD            
Sub-Investigator: Helene SUDOUR, MD            
Sub-Investigator: Cyril LERVAT, MD            
Centre Léon Bérard Recruiting
Lyon, France, 69373
Contact: Didier FRAPPAZ, MD     (33)478782642     frappaz@lyon.fnclcc.fr    
Sub-Investigator: Cécile CONTER, MD            
Sub-Investigator: Line CLAUDE, MD            
CHU, Hôpital d'Enfants de la Timone Recruiting
Marseille, France, 13385
Contact: J-Claude GENTET, MD     (33)491386821     jean-claude.gentet@ap-hm.fr    
Sub-Investigator: Nicolas ANDRE, MD            
Sub-Investigator: Arnauld VERSCHUUR, MD            
Sub-Investigator: Carole COZE, MD            
Sub-Investigator: Laetitia PADOVANI, MD            
Centre Hospitalier Universitaire de Nantes Recruiting
Nantes, France, 44093
Contact: Xavier RIALLAND, MD     (33)240083610     xavier.rialland@chu-nantes.fr    
Principal Investigator: Xavier RIALLAND, MD            
Sub-Investigator: Nicolas BLIN, MD            
Sub-Investigator: Nadege CORRADINI, MD            
Sub-Investigator: Marie-Laure COUEC, MD            
Sub-Investigator: Estelle LECULEE-THEBAUD, MD            
Sub-Investigator: Fanny RIALLAND, MD            
Sub-Investigator: Caroline THOMAS, MD            
Institut Curie Recruiting
Paris, France, 75231
Contact: Isabelle AERTS, MD     (33)144324551     isabelle.aerts@curie.net    
Sub-Investigator: François DOZ, PhD            
Sub-Investigator: Jean MICHON, MD            
Sub-Investigator: Daniel ORBACH, MD            
Sub-Investigator: Hélène PACQUEMENT, MD            
Sub-Investigator: Gudrun SCHLEIERMACHER, MD            
Sub-Investigator: Dominique LEVY, MD            
Sub-Investigator: Charline NORMAND, MD            
Sub-Investigator: Claire ALAPETITE, MD            
Sub-Investigator: Stéphanie BOLLE, MD            
Sub-Investigator: Frank BOURDEAUT, MD            
Hôpitaux Universitaires de Strasbourg Recruiting
Strasbourg, France, 67091
Contact: Natacha ENTZ-WERLE, MD     (33)3881280 91     natacha.entz-werle@chru-strasbourg.fr    
Sub-Investigator: Patrick LUTZ, PhD            
Sub-Investigator: Nadine COJEAN, MD            
Sub-Investigator: Izzie Jacques NAMER, MD            
Sub-Investigator: Georges NOEL, PhD            
CHRU Hôpital d'Enfants Recruiting
Vandoeuvre Les Nancy, France, 54511
Contact: Pascal CHASTAGNER, PhD     (33)383154621     p.chastagner@chu-nancy.fr    
Sub-Investigator: Fanny FOUYSSAC, MD            
Sub-Investigator: Ludovic MANSUY, MD            
Sub-Investigator: Aurélie PHULPIN-WEIBEL, MD            
Institut Gustave-Roussy Recruiting
Villejuif, France, 94805
Contact: Birgit GEOERGER, MD     (33)142114661     geoerger@igr.fr    
Sub-Investigator: Jacques GRILL, MD            
Sub-Investigator: Christelle DUFOUR, MD            
Sub-Investigator: Frederick DHERMAIN, MD            
Principal Investigator: Birgit GEORGER, MD            
Sub-Investigator: Angela Di GIANNATALE, MD            
Sponsors and Collaborators
Centre Oscar Lambret
Investigators
Principal Investigator: Pierre LEBLOND, MD Centre Oscar Lambret
  More Information

No publications provided

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01165333     History of Changes
Other Study ID Numbers: CILENT-0902
Study First Received: July 16, 2010
Last Updated: June 4, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Centre Oscar Lambret:
Paediatric oncology
Cilengitide
Glioma

Additional relevant MeSH terms:
Glioma
Pontine Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Astrocytoma

ClinicalTrials.gov processed this record on June 17, 2013