Lomustine With and Without Reirradiation for First Progression of Glioblastoma: a Randomized Phase III Study

A vizsgálat adatai

Ki végzi

European Organisation for Research and Treatment of Cancer - EORTC

Azonosító

NCT05904119EU 2023-505267-36-00

A regiszteradat frissítve

2026. június 8.

Eredeti leírás

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.A teljes eredeti leírásKevesebb

Despite comprehensive multimodal treatment of newly diagnosed glioblastoma, almost all patients suffer from tumour relapse. Currently, no standard of care exists to treat these tumour relapses. Treatment options include repeated surgery (if feasible), systemic therapy (bevacizumab, lomustine, temozolomide re-challenge), reirradiation and best supportive care. Currently, the superiority of combined chemoradiation versus chemotherapy alone remains unproven. Given that lomustine is the standard chemotherapeutic agent for the treatment of recurrent glioblastoma in Europe and the unclear efficacy of reirradiation, we want to explore whether combining lomustine and reirradiation may be a better treatment than lomustine alone. The results of the prospective randomized trial proposed here should demonstrate a significant improvement in overall survival when lomustine is combined with reirradiation in patients with recurrent glioblastoma compared to lomustine alone without adversely affecting quality of survival. The trial will be stopped based on overall survival in a preplanned futility and efficacy interim analysis.

Bevonási feltételek: Before patient's enrolment, written informed consent must be given according to ICH/GCP, and national/local regulations; Patients with first progression or recurrent glioblastoma after standard chemoradiotherapy (any treatment other than use of nitroureas) having occurred at least 6 months after the end of prior radiotherapy; Measurable disease according to RANO criteria with a maximum tumour diameter of 5 cm (local investigator assessment); In case of surgery for recurrence: fully recovered from surgery, confirmation of recurrence by histology, and patient fit for treatment as per local investigator assessment; Histologically proven diagnosis of glioblastoma, IDH wildtype per WHO 2021 classification and local assessment of tissue from diagnosis or recurrence; Initial treatment of newly diagnosed glioblastoma by maximal safe resection and postsurgical concurrent conventionally fractionated or abbreviated (minimum 15 fractions) chemoradiotherapy with or without maintenance chemotherapy with temozolomide (patient must have received at least one dose); Stable or decreasing dose of steroids for 7 days prior to enrolment; Age ≥ 18 years; WHO Performance status of 0-2; Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment; Patients of childbearing / reproductive potential must agree to use adequate birth control measures during the study treatment period and for at least 6 months after the last dose of study treatment. A highly effective method of birth control is defined as a method which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly; Female subjects who are breast feeding should discontinue nursing prior to the first dose of study treatment and until 6 months after the last study treatment; Non-sterile males must use contraception during treatment and for 6 months after the last dose; Non-sterile males must avoid sperm donation for the duration of the study and for at least 6 months after the last dose of study treatment.

Kizáró feltételek: Any prior anticancer treatment for recurrent glioblastoma (except surgery); Live attenuated vaccine in the 3 months prior to lomustine initiation; History or present acute leukaemia or any myeloid disease; Known hypersensitivity to the active components or excipients of lomustine; Known coeliac disease or wheat allergy; Any serious or uncontrolled medical condition (e.g., infections, chronic alcoholism, drug addiction) or abnormality, in the judgment of the investigator that prohibits obtaining informed consent, safe participation and study completion; Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed and discussed with the patient before the enrolment in the trial; Significant reduction in thrombocyte and/or leukocyte counts as well as severe renal impairment according to investigator's opinion; Known contraindication to imaging tracer or any product of contrast media and Magnetic Resonance Imaging (MRI) contraindications.

ClinicalTrials.gov NCT05904119 · EU CTIS 2023-505267-36-00