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Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Quality of Life

Patients with five or more brain metastasis assigned by randomization to Stereotactic RadioSurgery (SRS) or Stereotactic Body RadioTherapy (SBRT) will be treated with a highly-conformal metastasis-directed single dose between 15 and 24 Gy or fractionated dose (e.g. 27 Gy in 3 fractions), respectively, depending on lesion size, while sparing clinically negative brain. The treatment will be delivered using five non-coplanar arcs and a mono-isocentric technique.

Patients with five or more brain metastasis assigned by randomization to Whole Brain Irradiation (WBI) will be treated using a 3D-Conformal RadioTherapy technique for a uniform dose delivery of 30 Gy in 10 daily/fractions to the target, that is entire brain.

To treat only brain metastasis identified through Magnetic Resonance imaging by means of stereotactic radiotherapy (experimental intervention) to determine if sparing of clinically uninvolved brain implies a better neurocognitive performance, quality of life and level of autonomy in activities of daily living respect to Whole Brain Irradiation (active comparator).

Stereotactic RadioTherapy

To irradiate the entire brain, site of at least 5 parenchymal metastasis.

Whole Brain Irradiation

Gianluca Ferini

Irene R. Cravagno, Chief Radiation Oncology Unit

Anna Viola, Radiation Oncologist

Gianluca Ferini, Chief Radiation Oncology Unit

Vito Valenti

Antonella Tripoli

Silvana Parisi

Stefano Pergolizzi

Antonio Pontoriero

Alberto Cacciola

Sara Lillo

Gianluca Mortellaro

Giuseppe Ferrera

This work aims to evaluate neurocognitive performance, daily activity and quality of life and local control among patients with brain metastasis (MBM) ≥ 5 due to solid tumors treated with Stereotactic RadioSurgery (SRS) or Whole Brain RadioTherapy (WBRT). This multicentric randomised controlled trial will be conducted at the Fondazione IOM (Viagrande) in collaboration with REM (Viagrande), Hospital G. Martino (Messina) and Hospital Civico ARNAS (Palermo). It will involve, within 5 years starting from 15 September 2020, the enrollment of 100 patients (50 for each arm) with MBM ≥ 5, age ≥ 18 years, Karnofsky Performance Status (KPS) ≥ 70, life expectancy \> 3 months, histological confirmation of primary tumor, with controlled or controllable extracranial disease, baseline Montreal Cognitive Assessment (MoCA) of 20/30, Barthel Activities of Daily Living score 90/100, to be subjected to SRS on each brain lesion by LINAC with monoisocentric technique and non-coplanar arcs (experimental arm) or to WBRT (control arm). The primary endpoints are neurocognitive performance, quality of life and autonomy in daily-life activities variations, the first one assessed by Moca Score and Hopkins Verbal Learning Test - Revised, the second one through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care (EORTC QLQ-C15-PAL) and Brain Neoplasm (BN-20) questionnaires, the third one through the Barthel Index, respectively. The secondary endpoints are time to intracranial failure, overall survival, retreatments frequency, acute and late toxicities, KPS decrease. It will be considered significant a statistical difference of at least 29% between the two arms (statistical power of 80% with a significance level of 95%). This trial has been approved by the local ethics committee on July 7th 2020 (record 70). Several studies debate what is the predominant factor accountable for the development of neurocognitive decay among patients undergoing brain irradiation for MBM: radiotherapy, especially if extended to the entire brain, or intracranial disease progression? Answer to this question may come from current opportunity, thanks to recent technological advancement, to treat, with significant time savings, improved patient comfort and at the same time minimizing the dose to healthy brain tissue, Multiple Brain Metastasis simultaneously, otherwise attackable only by panencephalic irradiation. The pursuit of a local control rate comparable to that obtainable with WBRT remains the fundamental prerequisite for the aforementioned related assessments.

WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)

WHOle Brain Irradiation and STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER): a Prospective Comparative Study of Neurocognitive Outcomes, Level of Autonomy in Daily Activities and Quality of Life

To assess how neurocognitive performance changes after SRS/SBRT compared to WBI

To assess how level of autonomy in activities of daily living changes after SRS/SBRT compared to WBI

To assess how quality of life changes after SRS/SBRT compared to WBI

Time between treatment and cerebral disease progression detected through Magnetic Resonance imaging

Time from the first day of treatment to exitus

Difference in needing further subsequent radiotherapy treatment between SRS/SBRT and WBI arms

Toxicities registered within three months from treatment

Toxicities registered after three months from treatment

Evaluation of how patient's performance status modifies after treatment

University of Messina

University of Palermo

Mediterranean Institute of Oncology

Neoplasms, Second Primary

All Drugs and Chemicals

Antibodies

Immunoglobulins

131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT)

* Patients will be treated with WBRT administering a total dosage of 30 Gy in fractions of 3 Gy
* Dosimetric evaluation with 131I-L19SIP or 124I-L19SIP will be performed to assess eligibility for RIT.
* Patients eligible for RIT will receive a therapeutic dose of 131I-L19SIP.
* Total treatment duration is up to 4 weeks

Secondo Lastoria, Dr

Paul Mullholand, Dr

The aim of this Proof of Concept study is to determine the therapeutic potential of the L19SIP antibody, labeled with the radionuclide 131I in combination with external beam radiation, for the treatment of patients with multiple brain metastases following the promising results with this agent in previous clinical studies.

The L19SIP antibody is a fully human antibody, capable of preferential localization around tumor blood vessels while sparing normal tissues. The formation of new blood vessels is a rare event in the adult (exception made for the female reproductive cycle), but is a pathological feature in most aggressive types of cancer. The presented study follows a Phase I and a subsequent Phase I/II dose finding and efficacy study with the same agent in patients with a variety of cancers where 131I-L19SIP had shown an excellent tolerability and therapeutic benefit for some patients enrolled in the study.

131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors

A Prospective Non-randomized Study of 131I-L19SIP Radioimmunotherapy (RIT) in Combination With Whole Brain Radiation Therapy (WBRT) in Patients With Multiple Brain Metastases From Solid Tumors

Selective uptake of 131I-L19SIP or 124I-L19SIP in brain lesions

Safety will be assessed through physical examinations, vital signs, laboratory tests (including serum chemistries, hematology parameters) and the recording of adverse events. Treatment emergent adverse events will be summarized by CTCAE version 3 (and if possible by the RTOG/EORTG scale) and worse grade for all treated patients. Laboratory values and change in vital signs will be summarized.

Intracranial, extra cranial and overall response

GPA score will be assessed at the screening visit, during treatment and follow-up.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
WHOle Brain Irradiation or STEreotactic Radiosurgery for Five or More Brain Metastases (WHOBI-STER)	NCT04891471	Neurocognitive ... Quality of Life Activities of D...	Stereotactic Ra... Whole Brain Irr...	18 Years -	Mediterranean Institute of Oncology
131I-L19SIP Radioimmunotherapy (RIT) in Combination With External Beam Radiation in Patients With Multiple Brain Metastases From Solid Tumors	NCT01125085	Brain Metastase...	131I-L19SIP Rad...	18 Years -	Philogen S.p.A.

Spots Global Cancer Trial Database for multiple brain metastasis