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

Phase 3

Recruiting

• Conditions: Oligodendroglioma; Low-grade Oligodendroglioma; 1p19q Codeletion
• Interventions: Drug: Radiotherapy and PCV chemotherapy; Drug: PCV chemotherapy

• Registration Number: NCT04702581
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-01-07
• Study First Submitted QC: 2021-01-07
• Study First Posted: 2021-01-11
• Study Start: 2021-12-07
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-18
• Primary Completion: 2030-12
• Study Completion: 2030-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

• 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

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Exclusion Criteria

• 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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
RT + PCV	Radiotherapy and PCV chemotherapy	Radiotherapy followed by administration of PCV chemotherapy.
PCV alone	PCV chemotherapy	Administration of 6 cycles of PCV chemotherapy alone.

Primary Outcome Measures

Name	Time	Method
Survival without neurocognitive deterioration	During 9 years	Survival without neurocognitive deterioration (whatever the cause of deterioration, i.e toxicity or tumor progression) defined as the time from study randomization to failure in any of the 6 cognitive domains that will be explored (i.e memory, working memory, language, visuo-spatial ability, cognitive executive functions, behavioral executive functions) or death due to any cause, whichever occurs first.

Secondary Outcome Measures

Name	Time	Method
Progression free survival	During 9 years	Time from study randomization to the time of progression of the tumor
Overall survival	During 9 years	Time from study randomization to the time of death

Trial Locations

Locations (25)

Hôpital Saint-Louis, AP-HP; 🇫🇷 Paris, France

GH Pitié Salpêtrière; 🇫🇷 Paris, France

Hôpital Roger Salengro CHU de Lille; 🇫🇷 Lille, France

Hôpital Timone; 🇫🇷 Marseille, France

Institut de Cancérologie et Hematologie (ICH) - CHRU Brest, Hopital Morvan; 🇫🇷 Brest, France

CHU de Bordeaux Hôpital Saint André; 🇫🇷 Bordeaux, France

CHU de Caen; 🇫🇷 Caen, France

CHU d'Amiens-Picardie Site Sud; 🇫🇷 Amiens, France

Hôpital d'Instruction des Armées PERCY; 🇫🇷 Clamart, France

Centre Georges Francois Leclerc; 🇫🇷 Dijon, France

Institut de Cancerologie de l'Ouest; 🇫🇷 Saint-Herblain, France

CHU Saint-Etienne; 🇫🇷 Saint-Étienne, France

Hôpital Pasteur - Hôpitaux civils de Colmar; 🇫🇷 Colmar, France

CHU de Limoges; 🇫🇷 Limoges, France

Centre Léon Bérard; 🇫🇷 Lyon, France

CHU de Nice Hôpital Pasteur; 🇫🇷 Nice, France

CH Annecy Genevois site Annecy; 🇫🇷 Pringy, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Institut de Cancérologie Strasbourg Europe; 🇫🇷 Strasbourg, France

Institut Universitaire du Cancer Toulouse Oncopole; 🇫🇷 Toulouse, France

Hôpital Foch; 🇫🇷 Suresnes, France

CHRU de Tours; 🇫🇷 Tours, France

Gustave Roussy; 🇫🇷 Villejuif, France

Hospices Civils de Lyon; 🇫🇷 Bron, France

Centre Eugène Marquis; 🇫🇷 Rennes, France