Diffuse Intrinsic Pontine GliomaPhase 1CILENTNCT01165333
Cilengitide in Combination With Irradiation in Children With Diffuse Intrinsic Pontine Glioma
A Phase 1 study testing Cilengitide dose escalation, Cilengitide and Concomitant radiotherapy in people with Diffuse Intrinsic Pontine Glioma, run by Centre Oscar Lambret at 9 sites in France.
Trial summary
The aim of the study is to determine the safety of Cilengitide in combination with radiation therapy. Read more about this study
- Who is it for?
- Ages 6 months to 21 years
- Conditions the study is for
- Diffuse Intrinsic Pontine Glioma
- What is being tested?
- Cilengitide dose escalation, Cilengitide and Concomitant radiotherapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 9 sitesFrance
- Study dates
- 6 Sep 2010to Mar 2015
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
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- 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
- 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)
Who cannot join
None listed.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
France9 sites
Hôpital des Enfants, Groupe Hospitalier
Bordeaux, 33076
Centre Oscar Lambret
Lille, 59020
Centre Léon Bérard
Lyon, 69373
CHU, Hôpital d'Enfants de la Timone
Marseille, 13385
Centre Hospitalier Universitaire de Nantes
Nantes, 44093
Institut Curie
Paris, 75231
Hôpitaux Universitaires de Strasbourg
Strasbourg, 67091
CHU
Toulouse, 33059
Institut Gustave-Roussy
Villejuif, 94805
About this study
Official title: Cilengitide (EMD121974) in Combination With Irradiation in Children and Young Adults With Newly Diagnosed Diffuse Intrinsic Pontine Glioma: Phase I Study
The aim of the study is to determine the safety of Cilengitide in combination with radiation therapy.
Read the 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
- Being tested
- Cilengitide dose escalation, Cilengitide, Concomitant radiotherapy, Pharmacokinetic, Pharmacogenetic
- Keywords
- Paediatric oncology, Cilengitide, Glioma
- Medical subject headings
- Diffuse Intrinsic Pontine Glioma, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cilengitide dose escalationDrug
Also called Cilengitidine
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
CilengitideDrug
Also called cilengitidine
Patients will be treated at the recommended dose in order to confirm the recommended cilengitide dose and to carry out the exploratory investigations
Concomitant radiotherapyRadiation
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.
PharmacokineticBiological
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.
PharmacogeneticBiological
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.
Exploratory investigationBiological
Evaluate the metabolic impact of the treatment with dynamic MRI (diffusion, perfusion, spectro), and with FDG-PETand sestamibi SPECT.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Drug: Cilengitide; Radiation: Concomitant radiotherapy; Biological: Pharmacokinetic; Biological: Pharmacogenetic; Biological: Exploratory investigation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 6 weeks of treatment
Secondary outcomes (4)
Safety profile of the Cilengitide
toxicities (NCI-CTCAE v4.0)
Measured: During all the study
study of the pharmacoKinetic profile of Cilengitide
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
Measured: Day 1 and 2 of first cycle
estimate efficacy in terms of response according to histopathology
WHO criteria
Measured: Every 3 cycles
Progression-free and overall survival
6-month-PFS overall survival
Measured: During all the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2010 (estimated)
- Study start6 Sep 2010
- Primary completionJan 2014
- Study completionMar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Intrinsic Pontine GliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Oscar Lambret
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Pierre LEBLOND, MD, Principal investigator, Centre Oscar Lambret
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165333
- Sponsor's protocol ID
- CILENT-0902
- Other IDs
- 2009-016870-33, 2009
- Acronym
- CILENT
- Status last verified
- Mar 2026
- First submitted
- 16 Jul 2010
- Last updated
- 16 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No