Evaluation of the addition of Everolimus to 177Lu-DOTATATE in the treatment of grades 2 and 3 refractory meningioma: a phase IIb clinical trial

Phase 1

• Conditions: meningioma; MedDRA version: 20.0Level: HLTClassification code: 10027196Term: Meningiomas malignant Class: 10029205; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: CTIS2023-508400-38-00
• Lead Sponsor: CHRU De Nancy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-18
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 28

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, •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, •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., •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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of combining everolimus-PRRT with 177Lu-DOTATATE on PFS-6 in grades 2 and 3 refractory meningioma.;Secondary Objective: To evaluate the efficacy of the everolimus- PRRT with 177Lu-DOTATATE combination on OS-12, tumor growth rate, and tolerance/toxicity, in grades 2 and 3 refractory meningioma. The impact of tumor dosimetry on PFS-6 and OS-12 will also be assessed, and the evolution of patients’ health related quality (HRQoL) of life over 6 months will be described.;Primary end point(s): PFS-6 from the start of treatment according to the RANO criteria