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

January 6, 2026 updated by: Maciej Harat

Randomized Evaluation of Neoadjuvant Stereotactic Radiosurgery (SRS) and Multi-fraction SRS Alone for the Treatment of Large Brain Metastases: A Polish Multicenter Trial Protocol

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The RENESANS trial compares the efficacy and safety of two treatment strategies for large brain metastases: neoadjuvant stereotactic radiosurgery (Neo-SRS) and multi-fraction stereotactic radiosurgery (mfSRS) alone. It is a prospective, two-arm, randomized (1:1), controlled, multicentric phase III trial conducted between September 30, 2025 and September 30, 2033 in multiple radiation oncology units in Poland.

Study participants are patients with cancer and a Karnofsky performance status (KPS) >60 who have at least one brain metastasis appropriate for resection, not previously treated with SRS, and measuring ≥2.5 cm and <6 cm in the largest dimension. The intervention arms are: (i) neoadjuvant SRS (a single dose of 12-16 Gy SRS); and (ii) mfSRS alone (30 Gy delivered in 5 fractions).

The primary outcome is the number of participants developing a central nervous system (CNS) composite event, defined as local recurrence of the treated lesions, symptomatic radiation necrosis of the treated lesions, or development of leptomeningeal disease. Secondary outcomes include overall survival (OS), progression-free survival (PFS), adverse events assessed according to NCI CTCAE version 5.0 criteria, and health-related quality of life (QoL) assessed using the EORTC QLQ-C30 and QLQ-BN20 questionnaires.

Study Type

Interventional

Enrollment (Estimated)

98

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Neoadjuvant SRS (Arm 1)
Neoadjuvant SRS
Procedure: Neoadjuvant Stereotactic Body Radiation Therapy (SBRT)
Single dose of 12-16 Gy
Active Comparator: mfSRS alone (arm 2)
mfSRS alone
Procedure: Multi-fraction Stereotactic Body Radiation Therapy (SBRT)
30 Gy treatment in five fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central nervous system (CNS) composite event (CE)
Time Frame: From date of randomization to the date of a documented LR, SRN, or LMD, whichever comes first, assessed up to 12 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: From date of randomization to the date of death or 12 months, whichever comes first
OS is defined as the time between randomization and death due to any cause. Patients without an event will be censored at the date of last follow-up. Patients with no post-baseline follow-up for progression will be censored at the day of randomization. Median, six-month, and one-year OS will be measured
From date of randomization to the date of death or 12 months, whichever comes first
Progression-free survival (PFS)
Time Frame: From date of randomization to the date of death or 12 months, whichever comes first
PFS is defined as the time from randomization until radiographic progression, based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria (including local recurrence and distant brain metastases), or death from any cause. Patients without an event will be censored at the date of last progression-free follow-up. Patients without post-baseline follow-up will be censored at the date of randomization. Median, 6-month, and 1-year PFS will be reported.
From date of randomization to the date of death or 12 months, whichever comes first
Incidence of adverse events (any grade)
Time Frame: From date of randomization to the date of death or 12 months, whichever occurs first
All treatment-related adverse events (AEs) will be recorded from screening until disease progression or death. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. The number and proportion of participants experiencing at least one adverse event of any grade will be summarized by treatment arm.
From date of randomization to the date of death or 12 months, whichever occurs first
Incidence of grade ≥3 adverse events
Time Frame: From date of randomization to the date of death or 12 months, whichever occurs first.
The number and proportion of participants experiencing at least one treatment-related adverse event of grade 3 or higher, as defined by NCI CTCAE version 5.0, will be compared between treatment arms.
From date of randomization to the date of death or 12 months, whichever occurs first.
Health-related quality of life (EORTC QLQ-C30)
Time Frame: From date of randomization to the date of death or 12 months, whichever occurs first
Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Scores will be calculated according to the EORTC scoring manual and reported on a standardized scale from 0 to 100.
From date of randomization to the date of death or 12 months, whichever occurs first
Brain-specific quality of life (EORTC QLQ-BN20)
Time Frame: From date of randomization to the date of death or 12 months, whichever occurs first.
Brain cancer-specific quality of life will be assessed using the EORTC Brain Cancer Module (QLQ-BN20). Scores will be calculated according to the EORTC scoring manual and reported on a standardized scale from 0 to 100.
From date of randomization to the date of death or 12 months, whichever occurs first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Maciej Harat

Collaborators

Bydgoszcz University of Science and Technology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 1, 2026

Primary Completion (Estimated)

September 1, 2029

Study Completion (Estimated)

September 1, 2032

Study Registration Dates

First Submitted

September 2, 2025

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 9, 2026

Study Record Updates

Last Update Posted (Actual)

January 9, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RENESANS01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All IPD collected during the trial, after deidentification.

IPD Sharing Time Frame

After publication, no end date.

IPD Sharing Access Criteria

Anyone who wishes to access the data.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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