E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment with azacitidine of recurrent gliomas with IDH1/2 mutation after conventional treatments (radiotherapy and alkylant chemotherapy) |
Patients ayant un gliome avec mutation IDH1/2, en rechute après traitement conventionnel (radiothérapie et 1 ligne de chimiothérapie alkylante) |
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E.1.1.1 | Medical condition in easily understood language |
Brain tumor |
Tumeur cérébrale |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018338 |
E.1.2 | Term | Glioma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study will be to evaluate the efficacy based on Radiologic Assessment in Neuro-Oncology (RANO) criteria, of azacitidine in patients with recurrent IDH1/2 mutated glioma after conventional treatments.
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NA |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the clinical efficacy: objective response rateafter 6 cycles of treatment, overall survival - To evaluate the safety and tolerability of azacitidine.
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NA |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Evaluer l'effet déméthylant chez les patients candidats à une ré-intervention au cours de la recherche. |
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E.3 | Principal inclusion criteria |
1) Age > or equal 18 years 2) Glioma grade II or III with IDH1 or IDH2 mutation 3) Recurring after standard treatment, ie radiotherapy and alkylant chemotherapy, or alkylant chemotherapy alone in case of gliomatosis cerebri 4) For the patients treated by radiotherapy, recurrence occurring more than three months from the end of the radiotherapy or occurring outside the irradiated volume 5) Karnofsky performans status >50 6) Life expectancy > 9 months 7) Living within the geographic perimeter of the APHP home hospitalization center (departments 75,92,93,94) 8) Suitable laboratory values obtained ? 7 days before inclusion visit: - Absolute neutrophil count (ANC) ?1500 /mm3 - Leucocytes > or equal 3,0 x 109/L - Platelet count > or equal 75 000 / mm3 - Hemoglobin > 9.0 g/dL - SGOT (AST) < or equal 3 x ULN - SGPT (ALT) < or equal 3 x ULN - Uremia < or equal 1.5 x ULN - Creatininemia < or equal 1.5 x ULN - Bicarbonates > or equal 22 mmol/l 9) Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) must : o Have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. o Agree to use, and to be able to comply with, effective contraception without interruption, throughout the entire duration study drug therapy (including doses interruptions) and for 3 months after the end of the study drug therapy. 10) Male patients : o must agree to use a condom if engaged in sexual activity with a woman of childbearing potential during the entire period of treatment and during 3 months after end of treatment. o are informed about the procedures for preservation of sperm before starting treatment. 11) Written informed consent dated and signed, prior to any study specific procedures (sampling, treatment and analyses). 12) Affiliation to the french health insurance (recipient or assign)
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1) Age > ou égal à 18 ans 2) Gliome de grade II ou III avec mutation IDH1 ou IDH2 3) En rechute après traitement standard (radiothérapie et 1 ligne de chimiothérapie alkylante, ou chimiothérapie alkylante seule dans le cas de gliomatose cérébral) 4) Pour les patients traités par radiothérapie, rechute survenant plus de trois mois après la fin du traitement par radiothérapie ou apparue en dehors du volume irradié 5) Index de Karnofsky > 50 6) Espérance de vie > 9 mois 7) Résidant dans le périmètre géographique du centre hospitalisation à domicile de l'APHP (départements 75.92.93.94) 8) Paramètres biologiques adéquats (cf. §6.1) datant de moins d'une semaine avant l'inclusion : hémogramme, fonctions rénales et hépatiques, ionogramme sanguin 9) Pour les femmes en âge de procréer : - Test sanguin ou urinaire de grossesse négatif dans les 2 semaines précédant la 1e prise de traitement - Utilisation d'un moyen de contraception efficace pendant toute la durée du traitement et 3 mois après la dernière prise et 10) Pour les hommes, en couple avec une femme en âge de procréer : - Utilisation de préservatifs pendant toute la durée du traitement et 3 mois après la dernière prise - Informations reçues sur les mesures de préservation de fertilité avant le début du traitement 11) Signature du consentement éclairé 12) Affiliation à un régime de sécurité sociale (bénéficiaire ou ayant droit)
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E.4 | Principal exclusion criteria |
1) Breast-feeding women and pregnancy 2) Any evidence of severe or uncontrolled systemic diseases (as judged by the investigator), including uncontrolled hypertension, active bleeding diatheses, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) (Screening for chronic conditions is not required). 3) Active pulmonary disease or congestive cardiac insufficiency 4) Malignant hepatic tumor at a later stage 5) Intracranial hypertension or important deviation of the midline on the MRI 6) Any investigational agents or study drugs from a previous clinical study (within 30 days before the first dose of study treatment 7) Any chemotherapy, anticancer immunotherapy or anticancer agents within 4 weeks (6 weeks for nitrosourea) before the first dose of study treatment, 8) Any unresolved toxicities (excepted alopecia), from prior therapy greater than CTCAE grade 1 at the time of inclusion. 9) Known hypersensitivity to Azacitidine or Mannitol (E421), (refer to the Investigator's Brochure).
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1) Femme enceinte et allaitante 2) Maladie systémique sévère ou non controlée, incluant une hypertension artérielle incontrôlée, un syndrome hémorragique actif, ou une infection active dont hépatite B, hépatite C et virus de l'immunodéficience humaine (VIH). (Le dépistage des maladies chroniques n'est pas requis.) 3) Maladie pulmonaire active ou insuffisance cardiaque congestive 4) Tumeur hépatique maligne à un stade avancé 5) Hypertension intracranienne ou déviation importante de la ligne médiane sur l'IRM 6) Administration d'un médicament ou produit expérimental en rapport avec une précédente étude clinique dans les 30 jours précédant la première dose du traitement de l'essai 7) Administration d'une chimiothérapie, immunothérapie anticancéreuse ou médicament anticancéreux dans les 4 semaines (6 semaines pour les nitrosourées) précédant la première dose du traitement de l'essai 8) Toxicité non résolue (à l'exception de l'alopécie) d'une précédente thérapie, de grade CTCAE > 1 lors de l'inclusion 9) Hypersensibilité connue à l'azacitidine ou au Mannitol (E421) (refer to the Investigator's Brochure).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary assessment criterion will be Progression-Free Survival at 6 months (PFS-6) (24 weeks) estimated by the RANO criteria. PFS is defined as the time from first administration of study treatment to time of tumor progression or death due to any cause, whichever comes first. PFS-6 is the percentage of patients who have not progress 6 months after first administration of study treatment. |
NA |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6 cycles of treatment |
6 cycles de traitement |
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E.5.2 | Secondary end point(s) |
- The adverse events will be described and graded according to the revised NCI Common Terminology Criteria for Adverse Events (CTCAE V4.0) at each clinical visit, i.e every month until 1 month after the end of treatment. - Objective response rate at 6 months is defined by the percentage of patients with complete response and partial response using RANO criteria. - Overall survival is defined as the time from study registration to death due to any cause.
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NA |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
6 months, 1 year and until progression of the disease |
6 mois, 1 an et jusqu'à progression de la maladie |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS |
Dernier suivi du dernier patient |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |