Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Brain Neoplasms

Meningioma

Disease Attributes

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Trabectedin

Antineoplastic Agents, Alkylating

Alkylating Agents

Treatment in the control arm is left to the discretion of the investigator, according to the local standard of care.

Trabectedin will be given as a 24-hour infusion every 3 weeks at a starting dose of 1.5 mg/m2 body surface area (BSA), until one of the treatment withdrawal criteria has been met.

Left to the discretion of the investigator

Local standard of care

Matthias Preusser

The aim of this study is to collect data on activity, toxicity and quality of life of trabectedin therapy in patients with recurrent high-grade meningioma.

This is a randomized open label multicenter comparative phase II trial. The objective of the study is to investigate whether trabectedin demonstrates sufficient antitumor activity against recurrent grade II or III to justify further investigation in phase III or as adjuvant therapy for newly diagnosed disease after resection and radiotherapy.

Trabectedin for Recurrent Grade II/III Meningioma

Trabectedin for Recurrent Grade II or III Meningioma: a Randomized Phase II Study of the EORTC Brain Tumor Group

European Organisation for Research and Treatment of Cancer - EORTC

REGORAFENIB 40 mg tablets once daily (160 mg/die), 3 weeks on, 1 week off, until disease progression or unacceptable toxicity

Local Standard of Care until disease progression or unacceptable toxicity

Regorafenib 40 MG Oral Tablet

In this setting there are not drugs with indication. Every site will treat patients as per their experience.

Local Standard of Care

Gian Luca De Salvo, MD

Lorena Gurrieri, MD

Matteo Simonelli, MD

Valeria Internò, MD

Enrico Franceschi, MD

Isacco Desideri, MD

Elisa Bennicelli, MD

Anna Luisa Di Stefano, MD

Nicola Silvestris, MD

Paola Gaviani, MD

Giulia Berzero, MD

Bruno Daniele, MD

Silvia Chiesa, MD

Veronica Villani, MD

Giuseppe Minniti, MD

Roberta Rudà, MD

Giuseppe Lombardi, MD

The focus of this study will be to investigate whether Regorafenib demonstrates antitumor activity against recurrent grade II or III meningiomas.

Small trials and case series suggest clinical relevant activity of several VEGF inhibitors such as sunitinib, bevacizumab and valatinib reporting a 6m-PFS rate of 42-64%. Indeed, VEGF and VEGF receptors (VEGFR) are regularly overexpressed in meningiomas and can correlate with outcome.

Regorafenib inhibits angiogenic receptor tyrosine kinases (RTKs) and is highly selective for VEGFR1/2/3; moreover Regorafenib inhibits PDGFRB, FGFR1 and oncogenic intracellular signalling cascades involving c-RAF/RAF1 and BRAF highly expressed in meningiomas.

Noteworthy, Regorafenib showed antitumor activity in vitro and in vivo in a recent study; indeed, Regorafenib showed significant inhibition of meningioma cell motility and invasion and in vivo, mice with orthotopic meningioma xenografts showed a reduced volume of signal enhancement in MRI following Regorafenib therapy; this translated in a significantly increased overall survival time (p\<0.05) for Regorafenib treated mice.

Moreover, Regorafenib showed good efficacy in different cancer types, such as colorectal cancer, GIST, hepatocellular carcinoma and glioblastoma (REGOMA trial) , maintainingmaintaining a good quality of life.

Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial)

Regorafenib for Recurrent Grade 2 and 3 Meningioma. A Multicenter, Randomized Phase II Study (MIRAGE Trial)

The progression free survival (PFS) will be determined as the time from the date of enrolment to the date of disease progression determined using RANO criteria or to the date of death, whichever occurs first.

The overall survival (OS) will be determined as the time from the date of enrolment to the date of death from any cause.

The objective response rate (ORR) will be defined as the percentage of patients with complete response (CR) and partial response (PR) determined using modified Macdonald criteria.

Quality of life will be assessed by EORTC QLQ-C30 questionnaire.

Quality of life will be assessed by the QLQBN20 questionnaire.

Toxicity during the treatment will be recorded and graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v.5.

The disease control rate (DCR) will be defined as the percentage of patients with complete response (CR), partial response (PR) and stable disease (SD) determined using modified Macdonald criteria.

Bayer

Istituto Oncologico Veneto IRCCS

Gastrointestinal Agents

Antisickling Agents

Anti-Infective Agents

Bevacizumab

Everolimus

Lutetium Lu 177 dotatate

Sunitinib

Octreotide

Hydroxyurea

Angiogenesis Inhibitors

Growth Inhibitors

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Hormonal

Radiopharmaceuticals

According to local standard practice, treatment in the control arm is left to the investigator's discretion.

* Hydroxyurea
* Bevacizumab
* Sunitinib
* Octreotide (Sandostatin LAR)
* Everolimus
* No treatment (observation with regular follow-up and best supportive care)

Patients will receive 177Lu-DOTATATE with a total dose of 7.4 GBq/cycle every six weeks for four cycles as an IV infusion

According to local standard practice, treatment or no treatment in the control arm is left to the investigator's discretion.

Local standard of Care

177Lu-DOTATATE

EORTC

Nathalie Albert, Prof.

Novel treatments are urgently needed for meningiomas progressing after local therapies (surgery, radiotherapy). So far, no effective systemic therapies are known in this situation. The LUMEN-1 trial will investigate in a prospective randomized trial the efficacy of the precision medicine "theranostic" concept of combining diagnostic patient selection using PET-based molecular imaging and target-specific therapeutic intervention using a systemically administered radioligand.

The rationale for the LUMEN-1 trial is based on the following: (a) high somatostatin receptor (SSTR) expression in meningiomas, (b) wide-spread availability of clinically established SSTR-PET imaging, (c) proven efficacy of SSTR-targeting radioligand therapy using \[177Lu\]Lu-DOTATATE in another tumor type (neuroendocrine tumors), and (d) promising experiences with \[177Lu\]Lu-DOTATATE therapy in compassionate use applications and retrospective case series and interim results from one ongoing uncontrolled prospective trial in meningiomas. LUMEN-1 is the first randomized clinical trial to investigate \[177Lu\]Lu-DOTATATE therapy in refractory meningioma and may open new avenues for treatment and research in this area.

177Lu-DOTATATE for Recurrent Meningioma

177Lu-DOTATATE for Recurrent Meningioma: a Randomized Phase II Study

To examine whether \[177Lu\]Lu-DOTATATE demonstrates sufficient antitumor activity in patients with recurrent meningioma to justify further investigation. Progression-free survival computed based on MRI-based RANO meningioma response criteria as assessed by the local investigator.

Overall survival (OS), OS probability at 6 (OS6) and 12 months (OS12), median OS (mOS)

Best overall response (BOR, defined as CR, MR or PR during study treatment) rate. Complete response (CR) rate is computed by MRI based RANO meningioma response criteria as assessed by the local investigator.

Median best overall response (BOR, defined as CR, MR or PR during study treatment) duration. Median complete response (CR) duration is computed by MRI based RANO meningioma response criteria as assessed by the local investigator.

The magnitude of change in HRQoL in terms of global health status from EORTC QLQ-C30 during treatment.

The magnitude of change in HRQoL in terms of physical functioning from EORTC QLQ-C30 during treatment.

The magnitude of change in HRQoL in terms of motor disfunction from EORTC QLQ-BN20 during treatment.

Change of neurological function (NANO scale) from baseline during study treatment.

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trabectedin for Recurrent Grade II/III Meningioma	NCT02234050	Recurrent High ...	Trabectedin Local standard ...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial)	NCT06275919	Meningioma, Mal...	Regorafenib 40 ... Local Standard ...	18 Years -	Istituto Oncologico Veneto IRCCS
177Lu-DOTATATE for Recurrent Meningioma	NCT06326190	Recurrent Menin...	Local standard ... 177Lu-DOTATATE	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Trabectedin for Recurrent Grade II/III Meningioma	NCT02234050	Recurrent High ...	Trabectedin Local standard ...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
177Lu-DOTATATE for Recurrent Meningioma	NCT06326190	Recurrent Menin...	Local standard ... 177Lu-DOTATATE	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC

Spots Global Cancer Trial Database for local standard of care