Brain Cancer — Meningioma Clinical Trials

About Brain Cancer — Meningioma trials

Meningiomas are the most common primary tumor of the central nervous system, and about 80% are slow-growing CNS WHO grade 1 tumors managed with observation, surgery, or radiation rather than drug therapy. Systemic-therapy trials therefore concentrate on the harder subset: tumors that are progressive or recurrent, cannot be completely or safely resected, are not suitable for further radiation, or have CNS WHO grade 2 or 3 features. Grading is now partly molecular: under the 2021 WHO classification, homozygous deletion of CDKN2A/B or an oncogenic TERT promoter variant is sufficient for CNS WHO grade 3 regardless of the tumor's microscopic appearance. Roughly half of meningiomas have NF2 inactivation, affecting the tumor-suppressor protein merlin; these tumors are enriched at convexity and other non-midline locations and are more common among higher-grade tumors. NF2-wild-type meningiomas, many of which are lower-grade or arise at the skull base, may instead carry alterations in AKT1 (usually E17K), SMO, PIK3CA, TRAF7, or KLF4. These alterations are often distinct from NF2 inactivation but are not necessarily mutually exclusive with one another: AKT1, KLF4, and PIK3CA alterations can co-occur with TRAF7. Molecular testing generally uses archived or newly obtained tumor tissue from surgery or biopsy.

There is no FDA-approved systemic therapy specifically for meningioma, and most genotype-directed treatments remain investigational. NF2-altered tumors have been studied with focal adhesion kinase (FAK) inhibitors; SMO- or PTCH1-altered tumors with Hedgehog-pathway inhibitors; AKT1-, PIK3CA-, or PTEN-altered tumors with AKT inhibitors; and grade 2–3 tumors with NF2 or CDK-pathway alterations with CDK4/6 inhibitors. Alliance A071401 is a multi-arm umbrella trial that assigns patients with progressive meningioma to treatment according to these tumor alterations. Separately, meningiomas commonly express somatostatin receptor type 2, often reported as SSTR2A. This expression enables gallium-68 DOTATATE PET imaging and has led to studies of somatostatin analogs and peptide receptor radionuclide therapy (PRRT). Immune-checkpoint inhibitors and other systemic approaches are also being studied, particularly in recurrent or higher-grade disease. Because systemic treatments are not established as curative or standard therapy, clinical-trial enrollment is often preferred when surgery and radiation are no longer appropriate.

Across meningioma trials, eligibility usually turns first on CNS WHO grade and disease course; biomarker-directed studies may then require a particular molecular alteration or somatostatin-receptor expression. Studies commonly specify whether disease is newly diagnosed, residual, progressive, or recurrent and whether it is measurable on MRI. Many require documented growth over a defined interval. Some drug studies require prior surgery and radiation or a determination that further local treatment is inappropriate, although this is not universal. The date and extent of surgery, previous radiation dose and fields, treatment washout periods, and availability of suitable tumor tissue can all affect eligibility. Meningiomas use CNS WHO grades 1–3 rather than the AJCC stage I–IV framework used for many other solid tumors, so a numeric cancer stage should not be substituted for the trial's grade criteria. Performance status, adequate organ function, neurologic stability, and a stable or decreasing corticosteroid dose are also common requirements. Patients with the inherited condition now called NF2-related schwannomatosis, formerly neurofibromatosis type 2, may qualify for either general meningioma trials or dedicated studies.

Biomarkers tested in Brain Cancer — Meningioma trials

These are the molecular markers most commonly required or evaluated in Brain Cancer — Meningioma eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.