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

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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- 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.

Exclusion Criteria:

- Any prior anticancer treatment for recurrent glioblastoma (except surgery) - Significant reduction in thrombocyte and/or leukocyte counts as well as severe renal impairment according to investigator's opinion.

- 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.

- Live attenuated vaccine in the 3 months prior to lomustine initiation.

- 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.

- Known contraindication to imaging tracer or any product of contrast media and Magnetic Resonance Imaging (MRI) contraindications.

- 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05904119
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	European Organisation for Research and Treatment of Cancer - EORTC
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Matthias Preusser, Prof.Giuseppe Minniti, Dr.
Principal Investigator Affiliation	EORTC Study CoordinatorEORTC Study Coordinator
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	Austria, Belgium, Czechia, Denmark, France, Germany, Italy, Netherlands, Spain, Switzerland
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	First Progression of Glioblastoma

Arms & Interventions

Arms

Active Comparator: Control group

Lomustine alone

Experimental: Experimental group

Lomustine plus reirradiation

Interventions

Drug: - Lomustine

Oral administration of Lomustine

Radiation: - Reirradiation

Given at least 6 months after the end of prior radiotherapy

Contact a Trial Team

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International Sites

Innsbruck 2775220, Austria

Status

Recruiting

Address

A.O Landeskrankenhaus - Innsbruck Universitaetsklinik

Innsbruck 2775220, , 6020

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