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

ConditionMeningioma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-80
SponsorCentral Hospital, Nancy, France

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Other rapamycin derivatives (sirolimus, temsirolimus, deforolimus).

Other immunosuppressants

Trial design

Design model

Single group

Treatments tested in this trial

  • Everolimus

    Drug

    Patient will be treat during 7 months of Everolimus

Treatment groups

28 Participants
are divided into 1 treatment group
Group A: Patient treat with everolimusExperimental treatment 1 intervention

Trial outcomes

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)

Time frame
7 months

Secondary outcomes

1

Overall Survival

OS-12. Overall Survival, defined as the time from the date of inclusion to the date of death from any cause

Time frame
12 months
2

Tumor growth rate

Tumor growth rate, defined as the product of the two largest diameters of the target lesion from the MRI (Magnetic Resonance Imaging) at Month 3 or Month 6 compared to the diameters of the lesion at baseline.

Time frame
6 months
3

Progression Free Survival

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.

Time frame
1 month
4

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

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.

Time frame
180 days

Other outcomes

Sponsors and contacts

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