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

NCT06126588 | Recruiting Phase 2

• 1 other identifier: 2021PI203
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Meningioma

Outcome Measures

Primary Outcomes (1)

• RANO criteria (Response assessment in neuro oncology criteria)

  Progression Free Survival (PFS) from the start of treatment according to the RANO criteria (Response assessment in neuro oncology criteria)

  7 months

Secondary Outcomes (5)

• Overall Survival

  12 months

• Tumor growth rate

  6 months

• Progression Free Survival

  1 month

• Number and types of grade 1, 2, 3 or 4 adverse events according to the CTCAE

  180 days

• Questionnaire

  6 moniths

Study Arms (1)

Patient treat with everolimus

EXPERIMENTAL

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

Drug: Everolimus

Interventions

Everolimus DRUG

Patient will be treat during 7 months of Everolimus

Patient treat with everolimus

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead

Study Sites (2)

CHRU of Nancy

Vandœuvre-lès-Nancy, Grand Est, 54511, France

NOT YET RECRUITING

Nancy Hospital

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

MeSH Terms

Conditions

Meningioma

Interventions

Everolimus

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)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Antoine VERGER, MD,PhD

CONTACT

0383155567; a.verger@chru-nancy.fr

Caroline BOURSIER, MD

CONTACT

0383154039; c.boursier@chru-nancy.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 13, 2023
• Study Start: November 29, 2024
• Primary Completion: March 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 11, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)