177Lu-DOTATATE for Recurrent Meningioma

Inclusion Criteria:

• Adult patient ≥ 18 years of age

• Histologically confirmed diagnosis of meningioma (all grades, 1-3 per WHO CNS5, areeligible)

• WHO performance status 0-2

• Measurable disease (at least 10 x10 mm contrast enhancing lesion) on cranial MRI nomore than two weeks prior to randomization

• Radiologically documented progression of any existing tumour (growth > 25% in thelast two years) or appearance of new lesions (including intra- and extracranialmanifestations)

• Somatostatin receptor (SSTR)-positive confirmed by PET imaging with scan performedwithin four weeks before randomization (baseline SSTR-PET is considered as positivewhen meningioma uptake intensity exceeds a SUVmax of 2.3).

• At least one prior surgery and one line of external beam radiotherapy for meningioma

• Adequate liver, renal and haematological function within four weeks prior torandomization (1) Neutrophils ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dL or hemoglobin ≥ 5.6mmol/L, platelets ≥ 100 x 109/L, (2) Total Bilirubin ≤ 1 x ULN, SGPT/ALT andSGOT/AST ≤ 2.5 x ULN, (3) Albumin ≥ 30 g/L, (4) Serum creatinine ≤ 1.5 x ULN, (5)Creatinine clearance > 40 ml/min as calculated by CKD-EPI 2021

• Participants must have the following electrolyte values within normal limits orcorrected to be within normal limits with supplements prior to first dose of studymedication: (1) Potassium (potassium level of up to 6.0 mmol/L is acceptable atstudy entry if associated with creatinine clearance within normal limits calculatedusing CKD-EPI formula). Mild decrease below lower limit of normal (LLN) isacceptable at study entry if considered not clinically significant by investigator, (2) Magnesium, with the exception of magnesium level > ULN - 3.0 mg/dL (1.23 mmol/L)associated with creatinine clearance within normal limits calculated using CKD-EPIformula. Mild decrease below LLN is acceptable at study entry if considered notclinically significant by Investigator, (3) Total calcium (corrected for serumalbumin) level of up to 12.5 mg/dL (3.1 mmol/L) is acceptable at study entry ifassociated with creatinine clearance within normal limits calculated using CKD-EPIformula. Mild decrease below LLN is acceptable at study entry if considered notclinically significant by Investigator.

• Patients who are receiving corticosteroid treatment with dexamethasone, must betreated with a dose of ≤4 mg/day (or other corticosteroids equivalent dose) for aminimum of 7 days initiation of study treatment.

• Women of childbearing potential (WOCBP) must have a negative serum (or urine)pregnancy test within 72 hours prior to randomization. A positive urine pregnancytest result must immediately be confirmed using a serum test. A pregnancy test is tobe reported within 7 days prior to the first dose of the study treatment. Note:women of childbearing potential are defined as premenopausal females capable ofbecoming pregnant (i.e., females who have had any evidence of menses in the past 12months, with the exception of those who had prior hysterectomy). However, women whohave been amenorrhoeic for 12 or more months are still considered to be ofchildbearing potential if the amenorrhea is possibly due to prior chemotherapy,antioestrogens, low body weight, ovarian suppression, or other reasons.

• Patients of childbearing / reproductive potential should use adequate birth controlmeasures during the study treatment period and for at least 6 months after the lastdose of treatment. A highly effective method of birth control is defined as a methodwhich results in a low failure rate (i.e., less than 1% per year) when usedconsistently and correctly. Such methods include: (1) Combined (oestrogen andprogestogen containing) hormonal contraception associated with inhibition ofovulation (oral, intravaginal, transdermal), (2) Progestogen-only hormonalcontraception associated with inhibition of ovulation (oral, injectable,implantable), (3) Intrauterine device (IUD), (4) Intrauterine hormone-releasingsystem (IUS), (5) Bilateral tubal occlusion, (6) Vasectomized partner, (7) Sexualabstinence (the reliability of sexual abstinence needs to be evaluated in relationto the duration of the clinical trial and the preferred and usual lifestyle of thepatient)

• Female subjects who are breast feeding should discontinue nursing prior to the firstdose of study treatment and until 7 months after the last study treatment.

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

Exclusion Criteria:

• Local therapy (surgery and / or radiotherapy) indicated per local investigator.Note: in case of patients with multiple meningioma lesions, in whom resection and /or radiotherapy of individual lesions is indicated, patients may be included afterlocal therapy (with a 4-week gap between surgery / end of radiotherapy and start oftreatment), if at least one remaining lesion fulfils the inclusion criteria.

• Any combined or any prior systemic treatment regardless the timing.

• Life expectancy is less than nine weeks.

• History of any other invasive malignancy within the last five years (exceptadequately treated non-melanoma skin cancer, clinically localized and very low-riskprostate cancer, and adequately treated cervical intraepithelial neoplasia)

• Suspected pregnancy or when pregnancy has not been excluded

• Contraindication to MRI, CT or PET

• Unstable cardiac conditions (congestive heart failure, angina pectoris, myocardialinfarction within one year before randomization, uncontrolled hypertension,clinically significant arrhythmias)

• Psychological, familial, sociological, or geographical conditions potentially hampercompliance with the study protocol and follow-up schedule.

• Known hypersensitivity to the active substance or to any excipients.