Upfront Bevacizumab/témozolomide for Gliomastomas With Neurological Impairment

Chemoradiotherapy Clinical Trial

— TEMOBEVA  

Official title:

Neo-adjuvant Treatment of Glioblastomas With Marked to Severe Neurological Impairment Using Upfront Bevacizumab/témozolomide Association Before an Eventual Radiotherapy. Multicentric Phase II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03623347
• Other study ID #: PI2011_843_0001
• Status: Completed
• Start date: January 1, 2011
• Est. completion date: May 12, 2017

Study information

• Verified date: August 2018
• Source: Centre Hospitalier Universitaire, Amiens
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 12, 2017
• Est. primary completion date: May 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chemoradiotherapy
• Glioblastoma

Intervention

Other:
• TMZ and BEV induction before chemoradiotherapy
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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire, Amiens

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Optimal chemoradiotherapy after upfront TMZ and BEV treatment.	The investigators reported here a series of patients in whom radiotherapy was considered as not feasible in first intention but most of which could be treated by optimal chemoradiotherapy after upfront TMZ and BEV treatment. The investigators analyzed the impact of this induction strategy on tumor and target volumes, neurological status and survival.	4-months