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

Oligodendroglioma Clinical Trial

— POLO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04702581
• Other study ID #: 69HCL20_0073
• Secondary ID: 2020-A02646-33
• Status: Recruiting
• Phase: Phase 3
• Start date: December 7, 2021
• Est. completion date: December 2030

Study information

• Verified date: March 2024
• Source: Hospices Civils de Lyon
• Contact: François DUCRAY, MD, PhD
• Phone: +33(0) 4 72 35 78 06
• Email: francois.ducray[@]chu-lyon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 280
• Est. completion date: December 2030
• Est. primary completion date: December 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• 1p19q Codeletion
• Low-grade Oligodendroglioma
• Oligodendroglioma

Intervention

Drug:
• PCV chemotherapy
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.
• 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

Locations

Country	Name	City	State
France	CHU d'Amiens-Picardie Site Sud	Amiens
France	Institut de Cancerologie de l'Ouest	Angers
France	CHU de Bordeaux Hôpital Saint André	Bordeaux
France	Institut de Cancérologie et Hematologie (ICH) - CHRU Brest, Hopital Morvan	Brest
France	Hospices Civils de Lyon	Bron
France	CHU de Caen	Caen
France	Hôpital d'Instruction des Armées PERCY	Clamart
France	Hôpital Pasteur - Hôpitaux civils de Colmar	Colmar
France	Centre Georges Francois Leclerc	Dijon
France	Hôpital Roger Salengro CHU de Lille	Lille
France	CHU de Limoges	Limoges
France	Centre Léon Bérard	Lyon
France	Hôpital Timone	Marseille
France	CHU de Nice Hôpital Pasteur	Nice
France	GH Pitié Salpêtrière	Paris
France	Hôpital Saint-Louis, AP-HP	Paris
France	CH Annecy Genevois site Annecy	Pringy
France	Centre Eugène Marquis	Rennes
France	Centre Henri Becquerel	Rouen
France	CHU Saint-Etienne	Saint-Étienne
France	Institut de Cancerologie de l'Ouest	Saint-Herblain
France	Institut de Cancérologie Strasbourg Europe	Strasbourg
France	Hôpital Foch	Suresnes
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
France	CHRU de Tours	Tours
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival without neurocognitive deterioration	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.	During 9 years
Secondary	Progression free survival	Time from study randomization to the time of progression of the tumor	During 9 years
Secondary	Overall survival	Time from study randomization to the time of death	During 9 years