Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial

NCT ID: NCT06126588

Last Updated: 2025-03-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-29
• Study Completion Date: 2028-05-01

Brief Summary

Meningioma, the most common intracranial primary tumor of the central nervous system predominantly affects people in their fifties. Meningiomas are generally subdivided into two entities: a priori non-aggressive meningiomas (grade 1), and meningiomas at high risk of aggressive behavior (grade 2/atypical and 3/anaplastic). The current conventional treatments for meningioma are surgery and radiotherapy. When these treatments are no longer feasible, meningiomas are considered refractory irrespectively of grade, and in these rare entities, the therapeutic arsenal is reduced to the few treatments that have shown limited efficacy. Refractory, and particularly grades 2 and 3 meningiomas, have very poor prognoses with a progression-free survival at 6 months (PFS-6) of 26%. The European Response Assessment in Neuro-Oncology group (RANO) recommends that in any new, grades 2 and 3 meningioma, therapy that achieves a PFS-6 >30% in phase II trials be considered promising.

In Nuclear Medicine, Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE, currently used on a compassionate basis in refractory meningioma, deploys an octreotide-like effect, and appears very promising, with preliminary PFS-6 of 94% and an overall survival at 12 months (OS-12) of 88% in grade 1 meningioma. However, its PFS-6 is reduced to 28% with an OS-12 of 65% in WHO grades 2 and 3 meningioma. Recently the non-radiolabeled octreotide and everolimus combination however achieved a PFS-6 of 55% and an OS-12 of 75% in a population of 90% WHO grades 2 and 3 meningioma.

Detailed Description

Meningioma, the most common intracranial primary tumor of the central nervous system predominantly affects people in their fifties. Meningiomas are generally subdivided into two entities: a priori non-aggressive meningiomas (grade 1), and meningiomas at high risk of aggressive behavior (grade 2/atypical and 3/anaplastic). The current conventional treatments for meningioma are surgery and radiotherapy. When these treatments are no longer feasible, meningiomas are considered refractory irrespectively of grade, and in these rare entities, the therapeutic arsenal is reduced to the few treatments that have shown limited efficacy. Refractory, and particularly grades 2 and 3 meningiomas, have very poor prognoses with a progression-free survival at 6 months (PFS-6) of 26%. The European Response Assessment in Neuro-Oncology group (RANO) recommends that in any new, grades 2 and 3 meningioma, therapy that achieves a PFS-6 >30% in phase II trials be considered promising.

In Nuclear Medicine, Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE, currently used on a compassionate basis in refractory meningioma, deploys an octreotide-like effect, and appears very promising, with preliminary PFS-6 of 94% and an overall survival at 12 months (OS-12) of 88% in grade 1 meningioma. However, its PFS-6 is reduced to 28% with an OS-12 of 65% in WHO grades 2 and 3 meningioma. Recently the non-radiolabeled octreotide and everolimus combination however achieved a PFS-6 of 55% and an OS-12 of 75% in a population of 90% WHO grades 2 and 3 meningioma.

Our research hypothesis is that 177Lu-DOTATATE PRRT, a vector targeting somatostatin type 2 receptor (octreotide type) with a high-energy β-emitting radioactive label, when combined with everolimus, an mTOR protein inhibitor with radiosensitizing properties, will potentiate the effects of the non-radiolabeled octreotide + everolimus combination and increase PFS-6 in refractory grades 2 and 3 meningioma patients.

Conditions

Meningioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patient treat with everolimus

The product Everolimus is an oral drug.The dosage is 7.5 mg.

Group Type: EXPERIMENTAL

Everolimus

Intervention Type: DRUG

Patient will be treat during 7 months of Everolimus

Interventions

Everolimus

Patient will be treat during 7 months of Everolimus

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patient < 80 years old, who received a complete comprehensive briefing about the trial and signed the informed consent
• Eligible patient for compassional access program (National Multidisciplinary Neuro-Oncology board to Lutathera ® traitement
• WHO performance status ≤ 3
• Patient with grade 2 and 3 meningioma, substantiated by histology, not amenable to surgery or radiotherapy, with clinical or radiological progression
• Clinical deterioration or at least 10% of tumor growth rate, defined as the product of the two largest diameters of the target lesion within 6 months
• Expressing somatostatin receptors as determined by 68Ga-DOTATOC PET (lesion uptake ≥ liver uptake and/or 1.7 fold SUVpeak of the controlateral meninges).
• Patient that underwent a brain MRI and 68Ga-DOTATOC PET within the last 2 months.
• Effective contraception required for women of childbearing age.
• Patient with social security cover.

Exclusion Criteria

• Hypersensitivity to everolimus.
• Contraindication to 177Lu-DOTATATE: renal failure GFR<40 mL/min/1.73m2 (calculated by the CKD-Epi Formula), hepatic failure total bilirubin >3N, heart failure NYHA III or IV.

Patients should not take the following treatments:

• Other rapamycin derivatives (sirolimus, temsirolimus, deforolimus).
• Other immunosuppressants
• Co-administration with potent inhibitors and inducers of CYP3A4 and/or the multidrug efflux pump P-glycoprotein (PgP) : Ketoconazole , itraconazole, posaconazole, voriconazole, telithromycin, clarithromycin, Nefazodone, Ritonavir, atazanavir, saquinavir, darunavir, indinavir, nelfinavir.
• If everolimus is taken with orally administered CYP3A4 substrates with a narrow therapeutic index (e.g. pimozide, terfenadine, astemizole, cisapride, quinidine or ergot alkaloid derivatives), the patient should be monitored for undesirable effects described in the product information of the orally administered CYP3A4 substrate.
• Contraindication to MRI or 68Ga-DOTATOC PET/CT.
• Person referred to and L. 3212-1 and L. 3213-1 (psychiatric care).
• Women of childbearing age without effective contraception
• Patient unable to attend follow-ups over a 12-month period.
• Patients who participate in an interventional clinical research trial for the duration of the ELUMEN study.
• Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014.
• Pregnant woman, birthing or breastfeeding mother
• Minor (not emancipated)
• Adult subject to a legal protection measure (such as guardianship, conservatorship)
• Adult who is unable to give consent

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

Antoine VERGER

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

CHRU of Nancy

Vandœuvre-lès-Nancy, Grand Est, France

Site Status: NOT_YET_RECRUITING

Nancy Hospital

Vandœuvre-lès-Nancy, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Antoine VERGER, MD,PhD

Role: CONTACT

a.verger@chru-nancy.fr

0383155567 ext. +33

Caroline BOURSIER, MD

Role: CONTACT

c.boursier@chru-nancy.fr

0383154039 ext. +33

Facility Contacts

Anne-Sophie Hue

Role: primary

dripromoteur@chru-nancy.fr

Antoine Verger, MD PhD

Role: primary

a.verger@chru-nancy.fr

+33383155567

Anne-Sophie Hue

Role: backup

a.hue@chru-nancy.fr

+33383153475

Other Identifiers

2021PI203

Identifier Type: -

Identifier Source: org_study_id