A Randomized Trial of Delayed Radiotherapy in Patients Low-grade Oligodendrogliomas Requiring a Treatment Other Than Surgery

Inclusion Criteria:

• Tumor is co-deleted for 1p and 19q based and IDH-mutant (IDH1 or IDH2) according tolocal diagnosis

• Histological confirmation of low-grade oligodendroglioma by central pathologicalreview according to WHO 2016 classification

• Age ≥ 18 years

• Patients with one or several prior surgical procedure for a low-gradeoligodendroglioma and who undergo a resurgery are eligible if they have not receivedprior radiotheray or chemotherapy and if the last histological diagnosis is alow-grade oligodendroglioma prior use of specific HDI prohibitions is permitted

• Patients who undergo an initial follow-up after surgery or re-surgery are eligibleif there is no evidence of anaplastic transformation on MRI (no new contrastenhancement, no obvious modification of the growth rate)

• Patients requiring an oncological treatment other than surgery because of one ormore of the following characteristics:

• Progressive disease defined as documented growth prior to inclusion

• Symptomatic disease defined as the presence of neurological or cognitivesymptoms or refractory seizures defined as having both persistent seizuresinterfering with everyday life activities other than driving a car and threelines of anti-epileptic drug regimen had not worked, including at least onecombination regimen.

• Age ≥ 40 and any surgical therapy

• Age < 40 with prior and subtotal resection or biopsy (i.e., anything less thangross total resection)

• Willing and able to complete neurocognitive examination and the QOL

• Karnofsky performance status ≥ 60

• Laboratory values obtained between 21 days before inclusion andrandomization,respecting the following criteria:

• Absolute neutrophil count (ANC) ≥1500 /mm3

• Platelet count ≥100,000 / mm3

• Hemoglobin > 9.0 g/dL

• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

• SGOT (AST) ≤ 3 x ULN

• Negative serum or urine pregnancy test done ≤ 7 days prior to registration, forwomen of childbearing potential only.

• Provide informed written consent

Exclusion Criteria:

• Pregnant and nursing women

• Men or women of childbearing potential who are unwilling to employ adequatecontraception for up to 6 months following the completion of PCV.

• Received any prior radiation therapy or chemotherapy for any CNS neoplasm.

• Co-morbid systemic illnesses or other severe concurrent disease which would make thepatient inappropriate for entry into this study or interfere significantly with theproper assessment of safety and toxicity of the prescribed regimens.

• Concomitant serious immunocompromised status (other than that related to concomitantsteroids).

• Uncontrolled intercurrent illness or psychiatric illness/social situations thatwould limit compliance with study requirements.

• Receiving any other investigational agent which would be considered as a treatmentfor the primary neoplasm (except specific inhibitors of IDH)

• Other active malignancy within 5 years of registration. Exceptions: Non-melanoticskin cancer or carcinoma-in-situ of the cervix.

• Contra-indication to CCNU: hypersensitivity to CCNU, wheat allergy, association toyellow fever vaccin

• Contra-indication to Procarbazine: severe renal failure, severe hepatic failure,hypersensitivity to procarbazine, association to yellow fever vaccin

• Contra-indication to Vincristine: hypersensitivity to vincristine, neuromusculardisorder (for example demyelinating Charcot-Mary Tooth neuropathy), severe renalfailure, severe hepatic failure.

• Not depending from the french system of health assurance