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 (TEMOTRAD01)

Assistance Publique - Hôpitaux de Paris

Status and phase

Unknown

Phase 2

Conditions

Adult Brainstem Glioma

Treatments

Drug: Temozolomide

Study type

Interventional

Funder types

Other

Identifiers

NCT03932981

P160954J

2018-002654-79 (EudraCT Number)

Details and patient eligibility

About

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).

Full description

The goal of this study is to assess the impact (objective response) of first-line chemotherapy in infiltrative non-enhancing adult brainstem gliomas that are progressing in an infiltrative and non-threatening way. Upon progression, (radiotherapy) RT will be administered. Main inclusion criteria are:18 years of age or older/Karnofsky's Index over 50 /Non-enhancing lesion at MRI/Histologically proven infiltrating pattern of brainstem glioma except in case of formal contraindication to surgery determined via discussion of the case with expert neurosurgeons during a national webmeeting ((GLIome du TRonc de l'ADulte group (GLITRAD))/Clinical and/or radiological progression with an infiltrative but non-threatening pattern, warranting antitumoral treatment. The treatment delivered will be Temozolomide at a monthly standard dose of 150-200 mg/m2/day at day 1 to day 5 for a duration of treatment of 12 months. The study is a prospective single-arm phase II trial. Primary end point is objective response rate (radiographic and clinical response) to Temozolomide according to Response assessment in neuro-oncology criteria (RANO criteria). Secondary end points are histological pattern of adult brainstem gliomas/Molecular pattern of adult brainstem gliomas/ Radiological pattern of adult brainstem gliomas based on standard and multimodal MRI/Metabolic pattern of adult brainstem gliomas based on 18F-DOPA PET CT at initial diagnosis and its change after treatment /Global survival/Quality of life questionnaire (EORTC QLQ-C30 with BN-20)/Tolerance to temozolomide/Volumetric velocity of the tumor growth during follow-up before treatment from the initial MRI until the last MRI before beginning of the treatment, established with sagittal cube FLAIR sequences/Volumetric velocity of the tumor growth during follow-up during treatment of chemotherapy, established with sagittal cube FLAIR sequences/Rate of objective response, stabilization and progression under treatment obtained by combining the RANO criteria and the scores obtained on 3 scales (ataxia measured by the Scale for the Assessment and Rating of Ataxia (SARA), diet measured by the Functional Oral Intake Scale (FOIS) and diplopia).A number of 60 patients should be enrolled. THe duration of the study is 4 years.

Enrollment

60 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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