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

Inclusion Criteria:

• Before patient's enrolment, written informed consent must be given according toICH/GCP, and national/local regulations.

• Patients with first progression or recurrent glioblastoma after standardchemoradiotherapy (any treatment other than use of nitroureas) having occurred atleast 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 ofrecurrence by histology, and patient fit for treatment as per local investigatorassessment.

• Histologically proven diagnosis of glioblastoma, IDH wildtype per WHO 2021classification and local assessment of tissue from diagnosis or recurrence

• Initial treatment of newly diagnosed glioblastoma by maximal safe resection andpostsurgical concurrent conventionally fractionated or abbreviated (minimum 15fractions) chemoradiotherapy with or without maintenance chemotherapy withtemozolomide (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 testwithin 7 days prior to the first dose of study treatment.

• Patients of childbearing / reproductive potential must agree to use adequate birthcontrol measures during the study treatment period and for at least 6 months afterthe last dose of study treatment. A highly effective method of birth control isdefined as a method which results in a low failure rate (i.e., less than 1% peryear) when used consistently and correctly.

• Female subjects who are breast feeding should discontinue nursing prior to the firstdose 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 thelast dose.

• Non-sterile males must avoid sperm donation for the duration of the study and for atleast 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 renalimpairment 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 prohibitsobtaining informed consent, safe participation and study completion

• Known contraindication to imaging tracer or any product of contrast media andMagnetic Resonance Imaging (MRI) contraindications

• Any psychological, familial, sociological or geographical condition potentiallyhampering compliance with the study protocol and follow-up schedule; thoseconditions should be assessed and discussed with the patient before the enrolment inthe trial.