Evaluation of Neoadjuvant Stereotactic Radiosurgery (SRS) and Multi-fraction SRS Alone for the Treatment of Large Brain Metastases

NCT07329634 | Not Yet Recruiting Phase 3

• 1 other identifier: RENESANS01
• Study Type: interventional
• Target: 98
• Locations: 0 countries
• Sites: N/A

Brief Summary

The prospective, two-arm, randomized, controlled, multicentric phase III RENESANS trial is designed to compare the efficacy and safety of neoadjuvant stereotactic radiosurgery (Neo-SRS) versus multi-fraction stereotactic radiosurgery (mfSRS) in patients with large brain metastases, with the primary objective of evaluating the incidence of central nervous system composite events.

Conditions

Brain Metastasis

Keywords

Brain metastasis; Stereotactic radiosurgery; Neoadjuvant therapy; Multi-fraction therapy

Outcome Measures

Primary Outcomes (1)

• Central nervous system (CNS) composite event (CE)

  Number of participants experiencing a central nervous system (CNS) composite event (CE). A CNS CE is defined as the occurrence of at least one of the following events: local recurrence (LR) of a treated lesion, symptomatic radiation necrosis (SRN) of a treated lesion, or development of leptomeningeal disease (LMD). This is a composite endpoint analyzed as a single binary outcome per participant.

  From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 12 months

Secondary Outcomes (6)

• Overall survival (OS)

  From date of randomization to the date of death or 12 months, whichever comes first

• Progression-free survival (PFS)

  From date of randomization to the date of death or 12 months, whichever comes first

• Incidence of adverse events (any grade)

  From date of randomization to the date of death or 12 months, whichever occurs first

• Incidence of grade ≥3 adverse events

  From date of randomization to the date of death or 12 months, whichever occurs first.

• Health-related quality of life (EORTC QLQ-C30)

  From date of randomization to the date of death or 12 months, whichever occurs first

Study Arms (2)

Neoadjuvant SRS (Arm 1)

EXPERIMENTAL

Neoadjuvant SRS

Procedure: Neoadjuvant Stereotactic Body Radiation Therapy (SBRT)

mfSRS alone (arm 2)

ACTIVE COMPARATOR

mfSRS alone

Procedure: Multi-fraction Stereotactic Body Radiation Therapy (SBRT)

Interventions

Neoadjuvant Stereotactic Body Radiation Therapy (SBRT) PROCEDURE

Single dose of 12-16 Gy

Neoadjuvant SRS (Arm 1)

Multi-fraction Stereotactic Body Radiation Therapy (SBRT) PROCEDURE

30 Gy treatment in five fractions

mfSRS alone (arm 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years.
• At least one brain metastasis appropriate for resection and not previously treated with SRS.
• Lesions ≥2.5 cm and ≤6 cm in largest dimension.
• Index lesion(s) will be treated, as outlined in the treatment section of the protocol.
• Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate Neo-SRS, i.e., the ability to lie flat in a stereotactic head mask.
• Any non-index lesion or lesions for which there is no possible resection must measure ≤4.0 cm in maximal dimension on the contrast MRI or CT brain scan obtained ≤35 days prior to pre-registration. Unresected lesions will be treated with SRS or mfSRS.
• KPS \>60
• MRI confirms 1-10 lesions, one of which one is the index lesion. Each non-index lesion (up to nine) must measure ≤4 cm in maximal extent on contrast MRI and not otherwise require resection.
• Known active or history of invasive primary non-central nervous system (CNS) cancer based on a documented histopathological diagnosis within the past three years.
• Patient can tolerate surgery and SRS.
• History/physical examination within 14 days prior to registration.
• A negative urine or serum pregnancy test (in persons of childbearing potential, defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal for at least 12 consecutive months) within ≤14 days prior to registration.
• Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment during this study to prevent pregnancy.
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry.

You may not qualify if:

• No resectable lesion ≥2.5 cm.
• Unresectable \>4 cm lesion.
• Previous whole brain irradiation.
• Progressive brain lesion treated with SRS.
• Previous resection of brain metastases.
• Leptomeningeal disease.
• Lesion diameter \>6.0 cm, or more than 20 lesions in the brain.
• Required emergency decompressive surgery for life-threatening intracranial hypertension (with a preference towards adjuvant SRS/mfSRS protocols).
• Prior diagnosis of malignant brain tumor.
• Pediatric patients (age \<18 years), pregnant women, and patients who are unable to give informed consent will be excluded.

Sponsors & Collaborators

• Maciej Harat: lead
• Bydgoszcz University of Science and Technology: collaborator

MeSH Terms

Conditions

Brain Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Central Study Contacts

Maciej Harat, MBChB

CONTACT

+48 52 374 30 82; haratm@co.bydgoszcz.pl

Maciej Blok, MBChB

CONTACT

+48 52 374 30 80; blokm@co.bydgoszcz.pl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology

Study Record Dates

• First Submitted: September 2, 2025
• First Posted: January 9, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2032
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After publication, no end date.
• Access Criteria: Anyone who wishes to access the data.