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Upfront Bevacizumab/témozolomide for Gliomastomas With Neurological Impairment

Study Purpose

New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-basedn chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Clinical criteria:- - age> to 18 years.
  • - GBM de novo.
  • - Histological evidence is essential.
A minimum interval of 7 days is required between biopsy and neo-adjuvant therapy. A minimum interval of 15 days is required for open skull surgery and neo-adjuvant therapy.
  • - The insertion of patients is a WHO score 3 and 4 in relation to the neurological deficit is possible by definition.
  • - Biological criteria.
  • - Polynuclear neutrophils> 1500 / mm3.
  • - pads> 100,000 / mm3.
  • - SGOT <5 at the upper limit of normal (ULN) - bilirubin <1.5 x ULN.
  • - Creatinine <1.5 ULN.
  • - proteinuria <2 g / 24 hours.
  • - Forensic criteria.
  • - Patient with health insurance.
  • - consent signed by the patient if it is lucid, or by default by the person of trust.

Exclusion Criteria:

  • - 1.
Patients without neurological deficit (SN 0) or with moderate deficit (SN 1 or SN 2). 2. In case of initial neurological deficit SN 3-4, the interest of a decompression surgery must be discussed. If the surgery is unsuccessful, a corticosteroid test, at least 4 days, with at least 1.5 mg / kg / day of prednisone equivalent, must be performed. If surgery and / or corticosteroids allow to return to an SN 0-2 neurological score with return to an RPA III, IV or V class, the patient is not included and must be treated according to a conventional chemoradiotherapy regimen with temozolomide (Stupp schema). 3. Multifocal tumor or whose excessive volume does not allow to consider curative radiation therapy at a dose of 60 Gy. 3. History of chemotherapy, (including Gliadel) and / or radiotherapy. 4. Cerebral or intratumoral haemorrhage on diagnostic MRI. However, microhemorrhages, haemosiderin deposits or haemorrhages secondary to biopsy or surgery are not contraindications. 5. Concomitant serious uncontrolled pathology, including another evolving cancer 6. Uncontrolled infection 7. Uncontrolled Hypertension (PAS> 160 mm Hg) Despite Optimized Treatment 8. Coronary artery disease or unstable arterial disease. Evolutionary aneurysm. Myocardial infarction less than 6 months old. 9. Stroke or peripheral arterial disease less than 6 months old. 10. Heart Failure> NYHA Grade II 11. Haemorrhagiparous disease (hemophilia, Willebrandt ...) 12. History of hemoptysis less than 1 month old. 13. Pulmonary embolism less than 1 month old. 14. Anticoagulant or antiplatelet therapy in progress. If possible, these treatments should be stopped before inclusion after consultation with a cardiologist or angiologist. However, these treatments may be continued if their discontinuation is considered harmful and that the participation in the trial is considered beneficial for the patient with regard to the haemorrhagic risk incurred. 15. Surgical procedure (other than craniotomy or stereotactic biopsy) less than one month old or foreseeable surgery. 16. History of digestive fistula or intestinal perforation whose resolution is less than 6 months old. 17. Pregnant or lactating patient (contraception to be prescribed if necessary) 18. Known intolerance to bevacizumab or temozolomide

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03623347
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Centre Hospitalier Universitaire, Amiens
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Mathieu Boone, MD
Principal Investigator Affiliation CHU AMIENS
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Completed
Countries
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Chemoradiotherapy
Additional Details

New approaches are needed for patients newly diagnosed with bulky glioblastoma (GB) and/or with severe neurological impairment that cannot benefit from first line temozolomide (TMZ)-based chemoradiotherapy. Bevacizumab (BEV), an antiangiogenic anti-VEGF-R monoclonal antibody, has a rapid impact on tumor-related brain edema in recurrent GB. The present study reports the feasibility and efficacy of an induction treatment with TMZ and BEV to alleviate the initial neurological impairment and/or to reduce the tumor volume before a delayed chemoradiotherapy. The investigators retrospectively analyzed tumor and target volumes and clinical neurological status in 39 patients with bulky GB and/or with severe neurological impairment after an induction treatment combining TMZ and BEV. Neurological and radiological responses were assessed according to RANO criteria. Calculating gross tumor and clinical target volumes (GTV and CTV) was done at diagnosis and before radiotherapy. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan Meier methods. Safety was reported according to NCTCAE.

Contact Information

This trial has no sites locations listed at this time. If you are interested in learning more, you can contact the trial's primary contact:

For additional contact information, you can also visit the trial on clinicaltrials.gov.