Treatment with Vidaza of a brain tumor

Phase 1

Active, not recruiting

• Conditions: Treatment with azacitidine of recurrent gliomas with IDH1/2 mutation after conventional treatments (radiotherapy and alkylant chemotherapy); MedDRA version: 20.0Level: PTClassification code 10018338Term: GliomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-002822-35-FR
• Lead Sponsor: ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-02-22
• Last Update Posted: 22 April 2024

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 63

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)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 57
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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).

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. <br><br>;Secondary Objective: - To evaluate the clinical efficacy: objective response rateafter 6 cycles of treatment, overall survival<br>- To evaluate the safety and tolerability of azacitidine.<br>;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.;Timepoint(s) of evaluation of this end point: 6 cycles of treatment

Secondary Outcome Measures

Name	Time	Method
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.<br>- Objective response rate at 6 months is defined by the percentage of patients with complete response and partial response using RANO criteria.<br>- Overall survival is defined as the time from study registration to death due to any cause.<br>;Timepoint(s) of evaluation of this end point: 6 months, 1 year and until progression of the disease