Combining Everolimus and 177Lu-DOTATATE for treating refractory meningioma

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

This study is testing if combining two treatments, Everolimus and 177Lu-DOTATATE, can help adults with hard-to-treat meningioma tumors live longer without their cancer getting worse.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Central Hospital, Nancy, France (other)
• Locations: 2 sites (Vandœuvre-lès-Nancy, Grand Est and 1 other locations)
• Trial ID: NCT06126588 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Everolimus with 177Lu-DOTATATE in patients with grades 2 and 3 refractory meningioma, which are tumors that do not respond to standard treatments like surgery and radiotherapy. The study aims to evaluate the progression-free survival rate at six months, with a target of exceeding 30%, as recommended by the European Response Assessment in Neuro-Oncology group. Eligible participants must be adults under 80 years old with confirmed histology and specific imaging results indicating tumor progression. The trial is conducted at the Central Hospital in Nancy, France.

Who should consider this trial

Good fit: Ideal candidates are adults under 80 years old with grades 2 or 3 meningioma that has progressed and is not amenable to surgery or radiotherapy.

Not a fit: Patients with grade 1 meningiomas or those who are not expressing somatostatin receptors may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment combination could significantly improve survival outcomes for patients with aggressive meningiomas.

How similar studies have performed: While there have been promising results with similar approaches in treating grade 1 meningiomas, the efficacy in grades 2 and 3 remains less established.

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

Where this trial is running

Vandœuvre-lès-Nancy, Grand Est and 1 other locations

• CHRU of Nancy — Vandœuvre-lès-Nancy, Grand Est, France (NOT_YET_RECRUITING)
• Nancy Hospital — Vandœuvre-lès-Nancy, France (RECRUITING)

Study contacts

• Study coordinator: Antoine VERGER, MD,PhD

Conditions: Meningioma