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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01165333
First received: July 16, 2010
Last updated: March 6, 2014
Last verified: June 2012
  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

Resource links provided by NLM:


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: September 2014
Primary Completion Date: January 2014 (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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01165333

Locations
France
Hôpital des Enfants, Groupe Hospitalier
Bordeaux, France, 33076
Centre Oscar Lambret
Lille, France, 59020
Centre Léon Bérard
Lyon, France, 69373
CHU, Hôpital d'Enfants de la Timone
Marseille, France, 13385
Centre Hospitalier Universitaire de Nantes
Nantes, France, 44093
Institut Curie
Paris, France, 75231
Hôpitaux Universitaires de Strasbourg
Strasbourg, France, 67091
CHU
Toulouse, France, 33059
Institut Gustave-Roussy
Villejuif, France, 94805
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: March 6, 2014
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
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 28, 2014