| Eligibility |
Inclusion Criteria:
- Adult patient = 18 years of age
- Histologically confirmed diagnosis of meningioma (all grades, 1-3 per WHO CNS5, are
eligible)
- WHO performance status 0-2
- Measurable disease (at least 10 x10 mm contrast enhancing lesion) on cranial MRI no
more than two weeks prior to randomization
- Radiologically documented progression of any existing tumour (growth > 25% in the last
two years) or appearance of new lesions (including intra- and extracranial
manifestations)
- Somatostatin receptor (SSTR)-positive confirmed by PET imaging with scan performed
within four weeks before randomization (baseline SSTR-PET is considered as positive
when 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 to
randomization (1) Neutrophils = 1.5 x 109/L, hemoglobin = 9 g/dL or hemoglobin = 5.6
mmol/L, platelets = 100 x 109/L, (2) Total Bilirubin = 1 x ULN, SGPT/ALT and SGOT/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 or
corrected to be within normal limits with supplements prior to first dose of study
medication: (1) Potassium (potassium level of up to 6.0 mmol/L is acceptable at study
entry if associated with creatinine clearance within normal limits calculated using
CKD-EPI formula). Mild decrease below lower limit of normal (LLN) is acceptable 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-EPI formula. Mild
decrease below LLN is acceptable at study entry if considered not clinically
significant by Investigator, (3) Total calcium (corrected for serum albumin) level of
up to 12.5 mg/dL (3.1 mmol/L) is acceptable at study entry if associated with
creatinine clearance within normal limits calculated using CKD-EPI formula. Mild
decrease below LLN is acceptable at study entry if considered not clinically
significant by Investigator.
- Patients who are receiving corticosteroid treatment with dexamethasone, must be
treated with a dose of =4 mg/day (or other corticosteroids equivalent dose) for a
minimum 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 pregnancy test
result must immediately be confirmed using a serum test. A pregnancy test is to be
reported within 7 days prior to the first dose of the study treatment. Note: women of
childbearing potential are defined as premenopausal females capable of becoming
pregnant (i.e., females who have had any evidence of menses in the past 12 months,
with the exception of those who had prior hysterectomy). However, women who have been
amenorrhoeic for 12 or more months are still considered to be of childbearing
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 control
measures during the study treatment period and for at least 6 months after the last
dose of 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. Such methods include: (1) Combined (oestrogen and
progestogen containing) hormonal contraception associated with inhibition of ovulation
(oral, intravaginal, transdermal), (2) Progestogen-only hormonal contraception
associated with inhibition of ovulation (oral, injectable, implantable), (3)
Intrauterine device (IUD), (4) Intrauterine hormone-releasing system (IUS), (5)
Bilateral tubal occlusion, (6) Vasectomized partner, (7) Sexual abstinence (the
reliability of sexual abstinence needs to be evaluated in relation to the duration of
the clinical trial and the preferred and usual lifestyle of the patient)
- Female subjects who are breast feeding should discontinue nursing prior to the first
dose of study treatment and until 7 months after the last study treatment.
- Before patient 's enrolment, written informed consent must be given according to
ICH/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 after local
therapy (with a 4-week gap between surgery / end of radiotherapy and start of
treatment), 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 (except adequately
treated non-melanoma skin cancer, clinically localized and very low-risk prostate
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, myocardial
infarction within one year before randomization, uncontrolled hypertension, clinically
significant arrhythmias)
- Psychological, familial, sociological, or geographical conditions potentially hamper
compliance with the study protocol and follow-up schedule.
- Known hypersensitivity to the active substance or to any excipients.
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