Biological, targeted medicine for Diffuse Intrinsic Pontine Glioma treatment

Phase 1

• Conditions: Diffuse Intrinsic Pontine Glioma; MedDRA version: 20.0Level: PTClassification code 10006143Term: Brain stem gliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001929-32-GB
• Lead Sponsor: Gustave Roussy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-11-25
• Last Update Posted: 15 October 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

Eligibility criteria for the BIOMEDE study (pre-screening for the randomised subtrials)
- Diagnosis of DIPG (clinical and radiological, or histological in case the biopsy was performed before study entry)
- DIPG at diagnosis: no prior chemotherapy for the present cancer; no prior cerebral radiation therapy
- NB : Metastatic disease allowed. Patient with metastatic disease are eligible for the study (including the randomised trial if diagnosis of DIPG confirmed). In this situation, radiotherapy will have to start within three weeks after the biopsy while targerted treatment will start at the end of the irradiation
- Age > 6 months and < 25 years. For children below the age of 3 years, inclusion in the study and medical decisions should be discussed with the coordinating investigator.
- Eligible for a biopsy, or biopsy performed for diagnostic purpose and material available for the biomarker assessment
- Eligible for cerebral radiotherapy
- Patient covered by an health insurance if national requirement
- Written informed consent given by patient and/or parents/legal representative for biomarkers assessment and registration in the study.

Common eligibility criteria for the BIOMEDE randomised subtrials
- Eligibility criteria for the study (see above)
- Confirmed histological diagnosis of diffuse intrinsic pontine glioma (grade II, III, IV WHO), confirmed by central pathology review (including the assessment of the loss of H3K27me3 by immunohistochemistry or the presence of a mutation in the histone H3 variant genes). Patients without classical clinical and radiological diagnostic criteria who fulfil the histological and biological criteria of DIPG are eligible for the trial. Pilocytic astrocytoma and ganglioliomas are not eligible.
- Life expectancy > 12 weeks after the start of study treatment
- Karnofsky performance status scale or Lansky Play Scale > 50%. The PS should not take the neurologic deficit per se into account. NB: Children and young adults with a worse performance status due to glioma-related motor paresis can be included.
- Absolute neutrophil 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 NCI-CTCAE version 4.0 especially cardiovascular, pulmonary or renal disease (including but not limited to: congenital long QT syndrome, nephrotic syndrome, glomerulopathy, uncontrolled high blood pressure despite adequate treatment, interstitial lung disease, pulmonary arterial hypertension).In case of known or possible cardiac disease, a cardiological advice will be required prior to the inclusion in the randomized trial as a preexisting cardiopathy represents a contra-indication to dasatinib.
- Effective and appropriate contraception for patients (male and female) of reproductive potential during their entire participation in the study and during 6 months after the end of treatment. Effective contraception are defined in CTFG Guidelines Recommendations related to contraception and pregnancy testing in clinical trials”
- Negative pregnancy test (serum beta-HCG) evaluated in the last week in females of reproductive potential
- Written informed consent given by patient and

Exclusion Criteria

Non eligibility criteria for the study
- Massive intratumour bleeding
- Any other concomitant anti-cancer treatment not foreseen by this protocol
- Any other cancer during the last 5 years
- Uncontrolled intercurrent illness or active infection
- Any other co-morbid condition that in the investigator’s opinion would impair study participation
- Unable for medical follow-up (geographic, social or mental reasons)
- Patient not fulfilling one of the previous eligibility criteria.
- Patient previously treated with irradiation on the brainstem for another neoplasm
- Patient with congenital galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.
- Patient not covered by a social security agreement accepted in the treating country if national requirement.
- Pregnant or breast feeding women
- NB: A patient with known hypersensitivity for one the drug or its excipients could still participate to the study and receive one of the other drug(s)

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified