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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CHRU De Nancy

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

29 Nov 2024 → ongoing

Decision date (initial)

2024-04-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2023-508400-38-00

ClinicalTrials.gov

NCT06126588

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the efficacy of combining everolimus-PRRT with 177Lu-DOTATATE on PFS-6 in grades 2 and 3 refractory meningioma.

Secondary objectives 1

1. 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.

Conditions and MedDRA coding

meningioma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. • Adult patient < 80 years old, who received a complete comprehensive briefing about the trial and signed the informed consent
2. • Eligible patient for compassional access program (National Multidisciplinary Neuro-Oncology board to Lutathera ® traitement
3. • WHO performance status ≤ 3
4. • Patient with grade 2 and 3 meningioma, substantiated by histology, not amenable to surgery or radiotherapy, with clinical or radiological progression
5. • 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
6. • Expressing somatostatin receptors as determined by 68Ga-DOTATOC PET (lesion uptake ≥ liver uptake and/or 1.7 fold SUVpeak of the controlateral meninges).
7. • Patient that underwent a brain MRI and 68Ga-DOTATOC PET within the last 2 months.
8. • Effective contraception required for women of childbearing age.
9. • Patient with social security cover.

Exclusion criteria 15

1. • Hypersensitivity to everolimus
2. • Individuals referred to in Articles 10, 31, 32, 33 and 34 of Regulation (EU) No 536/2014.
3. • Pregnant woman, birthing or breastfeeding mother
4. • Minor (not emancipated)
5. • Adult subject to a legal protection measure (such as guardianship, conservatorship)
6. • Adult who is unable to give consent
7. • 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.
8. • 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.
9. • 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.
10. • Contraindication to MRI or 68Ga-DOTATOC PET/CT.
11. • Person referred to and L. 3212-1 and L. 3213-1 (psychiatric care).
12. • Women of childbearing age without effective contraception
13. • Patient unable to attend follow-ups over a 12-month period
14. • Patients who participate in an interventional clinical research trial for the duration of the ELUMEN study.
15. Patient receiving any systemic treatment for meningioma (bevacizumab, everolimus, cold octreotide, sunitinib, hydroxycarbamide)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. PFS-6 from the start of treatment according to the RANO criteria

Secondary endpoints 6

1. 1) OS-12. Overall Survival, defined as the time from the date of first administration of Luthatera to the date of death from any cause.
2. 2) Tumor growth rate, defined as the product of the two largest diameters of the target lesion from the MRI at M3 or M6 compared to the diameters of the lesion at baseline.
3. 3) PFS-6. Dose delivered to the tumor (dosimetry) will be calculated on at least 2 skull scans with 177Lu-DOTATATE SPECT-CT (D1 and D7), after the first cycle of 177Lu-DOTATATE.
4. 4) OS-12. Dose delivered to the tumor (dosimetry) will be calculated on at least 2 skull scans with 177Lu-DOTATATE SPECT-CT (D1 and D7), after the first cycle of 177Lu-DOTATATE.
5. 5) Number and types of grade 1, 2, 3 or 4 adverse events according to the CTCAE (Common Terminology Criteria for Adverse Events) classification per patient, from the start of treatment until 180 days after the end of the last treatment cycle.
6. 6) HRQoL, assessed using the EORTC QLQ-C30 questionnaire at inclusion (V1) and 6 months after Luthatera first administration (V8)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CHRU De Nancy

Sponsor organisation

CHRU De Nancy

Address

Co N°34, 29 Avenue Du Mal De Lattre De Tassigny, Bp 60034 29 Avenue Du Mal De Lattre De Tassigny Bp 60034

City

Nancy Cedex

Postcode

54035

Country

France

Scientific contact point

Organisation

CHRU De Nancy

Contact name

VERGER

Public contact point

Organisation

CHRU De Nancy

Contact name

VERGER

Locations

1 EU/EEA country · 12 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 34 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications