NCT03631953: ALTREM

Combination of Alpelisib and Trametinib in Progressive Refractory Meningiomas

Recruiting now Phase 1 Last updated 6 August 2024

What this trial tests

Phase 1 trial testing Trametinib in Meningioma in 25 participants. Currently enrolling.

Timeline

30 September 2019

Primary endpoint
29 January 2026

29 January 2026

Quick facts

Lead sponsor	Assistance Publique Hopitaux De Marseille
Phase	Phase 1
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	25
Start date	30 September 2019
Primary completion	29 January 2026
Estimated completion	29 January 2026
Sites	1 location across France

Drugs / interventions tested

• Trametinib (trametinib) — full drug profile →
• Alpelisib (alpelisib) — full drug profile →
• Blood sample — full drug profile →
• MRI — full drug profile →

Conditions studied

• Meningioma — all drugs for Meningioma →

Sponsor

Assistance Publique Hopitaux De Marseille — full company profile →

Who can join

18 and older, any sex, with Meningioma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Aggressive growing meningiomas resistant to multiple surgeries and radiotherapy constitute an unmet pharmaceutical need in neurooncology, leading to a fatal issue within a few months. Grade II-III meningiomas progression-free survival (PFS) 6 is at 10-15%. Median PFS grade III meningioma is approximate 3 years.

Alpelisib is a well-tolerated Phosphoinositide 3-kinase α (Pi3Kα) specific inhibitor. However, phosphatidylinositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) inhibition does not induce apoptosis in vitro and induces an antiproliferative effect without any radiologic response in most treated patients.

Trametinib, a mekinist (MEK) inhibitor is currently used in combined treatment for recurrent melanomas in clinical practice with a good clinical tolerance at 1-2 mg daily. In vitro, on meningioma primary cell culture, Trametinib induces cell apoptosis via caspase activity.

These results strongly suggest the relevance to combine Alpelisib and Trametinib in aggressive and recurrent meningiomas.

Alpelisib and Trametinib combination has not been studied to date, despite each drugs have been separately studied in phase 3.

Multicenter, open label, dose-finding phase I study of Alpelisib in combination with Trametinib administered at a fixed dose (1.5 mg daily), both drugs will be administered daily. Starting dose of Alpelisib will be 160mg/day and will be increased to 200mg/day or decreased to 120mg/day depending of grade 3-4 adverse events occurrence, to determine maximal tolerated dose (MTD) and recommended dose.

Primary Objective is to determine the safety profile and tolerability of Alpelisib and Trametinib given in combination in patients with aggressive and refractory meningiomas in terms of Dose-Limiting Toxicities (DLT, assessed during cycle 1).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting PI3K in cancer: mechanisms and advances in clinical trials.
   Yang J, Nie J, Ma X, Wei Y, et al · · 2019 · cited 1142× · PMID 30782187 · DOI 10.1186/s12943-019-0954-x
2. Meningioma: A Review of Epidemiology, Pathology, Diagnosis, Treatment, and Future Directions.
   Ogasawara C, Philbrick BD, Adamson DC. · · 2021 · cited 183× · PMID 33801089 · DOI 10.3390/biomedicines9030319
3. Meningioma: not always a benign tumor. A review of advances in the treatment of meningiomas.
   Maggio I, Franceschi E, Tosoni A, Nunno VD, et al · · 2021 · cited 100× · PMID 34015955 · DOI 10.2217/cns-2021-0003
4. Meningioma: A Review of Clinicopathological and Molecular Aspects.
   Huntoon K, Toland AMS, Dahiya S. · · 2020 · cited 96× · PMID 33194703 · DOI 10.3389/fonc.2020.579599
5. The emerging role of PI3K inhibitors for solid tumour treatment and beyond.
   Belli C, Repetto M, Anand S, Porta C, et al · · 2023 · cited 53× · PMID 36914722 · DOI 10.1038/s41416-023-02221-1
6. Emerging systemic treatment options in meningioma.
   Mair MJ, Berghoff AS, Brastianos PK, Preusser M. · · 2023 · cited 47× · PMID 36181606 · DOI 10.1007/s11060-022-04148-8
7. Recent Advances in Meningioma Immunogenetics.
   Al-Rashed M, Foshay K, Abedalthagafi M. · · 2019 · cited 39× · PMID 31970090 · DOI 10.3389/fonc.2019.01472
8. Intracranial meningiomas: an update of the 2021 World Health Organization classifications and review of management with a focus on radiation therapy.
   Yarabarla V, Mylarapu A, Han TJ, McGovern SL, et al · · 2023 · cited 31× · PMID 37675219 · DOI 10.3389/fonc.2023.1137849