Trial Title:
Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT ID:
NCT06126588
Condition:
Meningioma
Conditions: Official terms:
Meningioma
Everolimus
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Everolimus
Description:
Patient will be treat during 7 months of Everolimus
Arm group label:
Patient treat with everolimus
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.
Detailed description:
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.
Our research hypothesis is that 177Lu-DOTATATE PRRT, a vector targeting somatostatin type
2 receptor (octreotide type) with a high-energy β-emitting radioactive label, when
combined with everolimus, an mTOR protein inhibitor with radiosensitizing properties,
will potentiate the effects of the non-radiolabeled octreotide + everolimus combination
and increase PFS-6 in refractory grades 2 and 3 meningioma patients.
Criteria for 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
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
CHRU of Nancy
Address:
City:
Vandœuvre-lès-Nancy
Zip:
54511
Country:
France
Facility:
Name:
Nancy Hospital
Address:
City:
Vandœuvre-lès-Nancy
Zip:
54511
Country:
France
Contact:
Last name:
Antoine Verger, MD PhD
Phone:
+33383155567
Email:
a.verger@chru-nancy.fr
Contact backup:
Last name:
Anne-Sophie Hue
Phone:
+33383153475
Email:
a.hue@chru-nancy.fr
Start date:
October 1, 2024
Completion date:
May 1, 2028
Lead sponsor:
Agency:
Central Hospital, Nancy, France
Agency class:
Other
Source:
Central Hospital, Nancy, France
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06126588
