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

Официальное название

A Randomized Trial of Delayed Radiotherapy in Patients 1p/19q Codeleted Low-grade Oligodendrogliomas Requiring a Treatment Other Than Surgery

Обзор

Because of their prolonged survival, patients with 1p/19q-codeleted low-grade oligodendrogliomas treated with RT + PCV are at risk of neurocognitive deterioration. We make the hypothesis that withholding radiotherapy until tumor progression could reduce the risk of neurocognitive deterioration without impairing overall survival.

Вмешательства

• Препарат PCV chemotherapy
  1. cycle of PCV chemotherapy is given as: * Day 1: CCNU 110 mg/m2 orally; * Days 8 and 29: Vincristine 1.4 mg/m2 IV; * Days 8 to 21: Procarbazine 60 mg/m2 orally 6 cycles are given.
• Препарат Radiotherapy and PCV chemotherapy
  Radiotherapy will deliver 50.4 Gy in 28 fractions of 1.8 Gy using IMRT technique. Followed by 6 cycles of PCV chemotherapy 1 cycle of PCV is given as: * Day 1: CCNU 110 mg/m2 orally; * Days 8 and 29: Vincristine 1.4 mg/m2 IV; * Days 8 to 21: Procarbazine 60 mg/m2 orally

Первичные конечные точки

• Survival without neurocognitive deterioration [Срок оценки: During 9 years]

Вторичные конечные точки (2)

• Progression free survival [Срок оценки: During 9 years]
• Overall survival [Срок оценки: During 9 years]

Критерии участия

Критерии включения

• Tumor is co-deleted for 1p and 19q based and IDH-mutant (IDH1 or IDH2) according to local diagnosis
• Histological confirmation of low-grade oligodendroglioma by central pathological review according to WHO 2016 classification
• Age ≥ 18 years
• Patients with one or several prior surgical procedure for a low-grade oligodendroglioma and who undergo a resurgery are eligible if they have not received prior radiotheray or chemotherapy and if the last histological diagnosis is a low-grade oligodendroglioma prior use of specific HDI prohibitions is permitted
• Patients who undergo an initial follow-up after surgery or re-surgery are eligible if there is no evidence of anaplastic transformation on MRI (no new contrast enhancement, no obvious modification of the growth rate)
• Patients requiring an oncological treatment other than surgery because of one or more of the following characteristics:

• Progressive disease defined as documented growth prior to inclusion
• Symptomatic disease defined as the presence of neurological or cognitive symptoms or refractory seizures defined as having both persistent seizures interfering with everyday life activities other than driving a car and three lines of anti-epileptic drug regimen had not worked, including at least one combination regimen.
• Age ≥ 40 and any surgical therapy
• Age < 40 with prior and subtotal resection or biopsy (i.e., anything less than gross 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, for women of childbearing potential only.
• Provide informed written consent

Критерии исключения

• Pregnant and nursing women
• Men or women of childbearing potential who are unwilling to employ adequate contraception 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 the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Concomitant serious immunocompromised status (other than that related to concomitant steroids).
• Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm (except specific inhibitors of IDH)
• Other active malignancy within 5 years of registration. Exceptions: Non-melanotic skin cancer or carcinoma-in-situ of the cervix.
• Contra-indication to CCNU: hypersensitivity to CCNU, wheat allergy, association to yellow 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, neuromuscular disorder (for example demyelinating Charcot-Mary Tooth neuropathy), severe renal failure, severe hepatic failure.
• Not depending from the french system of health assurance

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Франция · 26 центров

• CHU d'Amiens-Picardie Site Sud — Amiens
• Institut de Cancerologie de l'Ouest — Angers
• CHU de Bordeaux Hôpital Saint André — Bordeaux
• Institut de Cancérologie et Hematologie (ICH) - CHRU Brest, Hopital Morvan — Brest
• Hospices Civils de Lyon — Bron
• CHU de Caen — Caen
• Hôpital d'Instruction des Armées PERCY — Clamart
• Hôpital Pasteur - Hôpitaux civils de Colmar — Colmar
• … и ещё 18 центров

Идентификаторы

NCT: NCT04702581 · 69HCL20_0073 · 2020-A02646-33

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗