First-line Chemotherapy With Temozolomide Alone for Non-enhancing Adult Brainstem Gliomas, With a Diffuse Subtype and Showing Clinical and/or Radiological Infiltrative Pattern of Progression

• Status: Recruiting
• Trial end date: 2023-09-30
• Target enrollment: 0
• Participant gender: All

Summary

This phase 2 study is a prospective cohort study. Chemotherapy alone will be proposed to adult patients suffering from a "low grade" brainstem glioma subtype showing infiltrative, non-threatening clinico-radiological progression. Patients will receive temozolomide at a monthly standard dose of 150-200 mg/m2/j J1-J5, will be clinically evaluated every month and will undergo radiological evaluation every 2 months. The duration of treatment will be 12 months. Then, the patients will be followed-up until progression, with clinical evaluations and MRI performed every 2-3 months. At the time of recurrence, treatment with focal radiation therapy will be administered (54 Gy in classical fractions).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Assistance Publique - Hôpitaux de Paris
• Treatments: Temozolomide

Criteria

Inclusion Criteria:

• 18 years of age or older

• Karnofsky's Index over 50

• Non-contrast lesion on MRI

• Histologically proven low grade brainstem glioma with 2 exceptions:

• formal contraindication to surgery determined via discussion of the case with expert neurosurgeons during a national webmeeting (GLITRAD)

• negative brainstem biopsy These two exceptions may lead to case-by-case inclusion despite the lack of a histologically-proven diagnosis if clinical and radiological evidence support such a diagnosis and if a very detailed systemic check-up, standardized by the GLITRAD group (spinal MRI, whole body CT, PET, LP (if feasible), blood inflammatory and infectious counts, biopsy of the salivary glands, etc) is negative and allows us to state that this diagnosis is highly probable

• Clinical and/or radiological progression with an infiltrative but non-threatening pattern, warranting antitumoral treatment

• Absolute neutrophil count > 1.5 x 109/l,

• Platelets > 100 x 109/l

• Total bilirubin < 1.5 × ULN,

• AST and ALT< 3 x ULN

• Effective contraception

• Negative pregnancy test (serum beta-HCG) in females of reproductive age

• Written informed consent

• Affiliation to a social security scheme

Exclusion Criteria:

• Pilocytic astrocytoma

• Ependymoma

• Lack of a histologically proven diagnosis or an uncertain diagnosis regarding the tumoral nature and/or glial nature of the lesion after the GLITRAD webmeeting and a very detailed checkup looking for diagnostic pitfalls

• Contrast enhancement on MRI

• Clinico-radiological data favoring a more aggressive lesion, such as a high grade glioma, even in the case of a "low grade glioma" diagnosis after biopsy, suggesting histological under-grading

• Previous radiotherapy or chemotherapy for this lesion

• Contraindication to Temozolomide (Hypersensitivity to Temozolomide, dacarbazine or severe myelosuppression)

• Contraindication to IRM (pacemaker, intraocular metallic foreign bodies, intracranial metal clips, non-removable hearing aids, neurostimulation electrodes ...)

• Contraindication to IASOdopa® (hypersensitivity)

• Severe renal insufficiency

• Concomitant serious illness unbalanced that may interfere with follow-up

• History of malignancy within 5 years (excluding basal cell carcinoma or in situ carcinoma of the cervix)

• Pregnancy or breastfeeding

• Predictable difficulty with follow-up

• Patient under legal protection measures