177Lu-DOTATATE for Recurrent Meningioma

NCT06326190 | Recruiting Phase 2 DMC

• 1 other identifier: EORTC-2334-BTG
• Study Type: interventional
• Target: 136
• Locations: 5 countries
• Sites: 12

Brief Summary

Novel treatments are urgently needed for meningiomas progressing after local therapies (surgery, radiotherapy). So far, no effective systemic therapies are known in this situation. The LUMEN-1 trial will investigate in a prospective randomized trial the efficacy of the precision medicine "theranostic" concept of combining diagnostic patient selection using PET-based molecular imaging and target-specific therapeutic intervention using a systemically administered radioligand. The rationale for the LUMEN-1 trial is based on the following: (a) high somatostatin receptor (SSTR) expression in meningiomas, (b) wide-spread availability of clinically established SSTR-PET imaging, (c) proven efficacy of SSTR-targeting radioligand therapy using \[177Lu\]Lu-DOTATATE in another tumor type (neuroendocrine tumors), and (d) promising experiences with \[177Lu\]Lu-DOTATATE therapy in compassionate use applications and retrospective case series and interim results from one ongoing uncontrolled prospective trial in meningiomas. LUMEN-1 is the first randomized clinical trial to investigate \[177Lu\]Lu-DOTATATE therapy in refractory meningioma and may open new avenues for treatment and research in this area.

Conditions

Recurrent Meningioma

Keywords

177Lu-DOTATATE; Meningioma; Recurrent Meningioma; Phase II

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  To examine whether \[177Lu\]Lu-DOTATATE demonstrates sufficient antitumor activity in patients with recurrent meningioma to justify further investigation. Progression-free survival computed based on MRI-based RANO meningioma response criteria as assessed by the local investigator.

  From the date of randomization till the date of disease progression or death (time till death is up to 2 years after patient enrolment in the study)

Secondary Outcomes (8)

• Overall Survival (OS)

  From the date of randomization till the date of death (time till death is up to 2 years after patient enrolment in the study)

• Radiological response rate

  From the date of randomization till the date of disease progression or death (time till death is up to 2 years after patient enrolment in the study)

• Radiological response rate

  From the date of randomization till the date of disease progression or death (time till death is up to 2 years after patient enrolment in the study)

• The magnitude of change in Health-related quality of life (HRQoL)

  From the date of randomization regardless of progression status up to 2 years after patient enrolment in the study.

• The magnitude of change in Health-related quality of life (HRQoL)

  From the date of randomization regardless of progression status up to 2 years after patient enrolment in the study.

Study Arms (2)

Control group: local standard of care (LOC)

ACTIVE COMPARATOR

According to local standard practice, treatment in the control arm is left to the investigator's discretion. * Hydroxyurea * Bevacizumab * Sunitinib * Octreotide (Sandostatin LAR) * Everolimus * No treatment (observation with regular follow-up and best supportive care)

Drug: Local standard of Care

Experimental group: 177Lu-DOTATATE

EXPERIMENTAL

Patients will receive 177Lu-DOTATATE with a total dose of 7.4 GBq/cycle every four (4) weeks for four (4) cycles as an IV infusion

Drug: 177Lu-DOTATATE

Interventions

Local standard of Care DRUG

According to local standard practice, treatment or no treatment in the control arm is left to the investigator's discretion.

Also known as: Hydroxycarbamide, Bevacizumab, Sunitinib, Octreotide (Sandostatin LAR), Everolimus, No active treatment (observation with regular follow-up and best supportive care)

Control group: local standard of care (LOC)

177Lu-DOTATATE DRUG

Intravenous injection of 177Lu-DOTATATE

Also known as: ¹⁷⁷Lu-DOTA0-TATE, Lutathera®, Lu oxodotreotide

Experimental group: 177Lu-DOTATATE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• Novartis: collaborator

Study Sites (12)

A.O Landeskrankenhaus - Innsbruck Universitaetsklinik

Innsbruck, 6020, Austria

RECRUITING

Universitaetskliniken der Uni Wien - Universitaetsklinikum Wien - AKH unikliniken

Vienna, 1090, Austria

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Centre Eugene Marquis

Rennes, 35042, France

RECRUITING

CHRU de Nancy - Hopitaux De Brabois

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Oslo University Hospital - Radiumhospitalet

Oslo, 0379, Norway

RECRUITING

St Olavs University Hospital - St. Olavs Hospital, Trondheim University Hospital

Trondheim, 7030, Norway

RECRUITING

Vall D Hebron - Hospital Universitari Vall d'Hebron -Vall d'Hebron Institut Oncologia

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 De Octubre

Madrid, 28041, Spain

RECRUITING

Oncology Institute of Southern Switzerland (IOSI) - Ospedale San Giovanni

Bellinzona, 6500, Switzerland

NOT YET RECRUITING

UniversitaetsSpital Zurich - Neurology Clinic

Zurich, 8091, Switzerland

NOT YET RECRUITING

MeSH Terms

Conditions

Meningioma

Interventions

Hydroxyurea; Bevacizumab; Sunitinib; Octreotide; Everolimus; Observation; lutetium Lu 177 dotatate

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Sirolimus; Macrolides; Lactones; Methods; Investigative Techniques

Study Officials

• Prof. Nathalie Albert

  EORTC Study Coordinator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

EORTC

CONTACT

+32 2 774 16 11; eortc@eortc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2024
• First Posted: March 22, 2024
• Study Start: March 10, 2025
• Primary Completion (Estimated): April 14, 2027
• Study Completion (Estimated): December 22, 2028
• Last Updated: September 16, 2025

Record last verified: 2025-09

Locations

FR (4); AU (2); NO (2); CH (2); ES (2)