Improving Therapeutic Ratio With Hypo Fractionated Stereotactic Radiotherapy for Brain Metastases (SAFESTEREO)

Randomized phase II trial. The study aims to investigate a different and potentially safer radio therapeutic treatment method for brain metastases. The current standard of stereotactic radiotherapy (SRT) in one or three fractions is compared to fractionated stereotactic radiotherapy (fSRT) in five fractions.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: SRT; Radiation: fSRT

Detailed Description

Randomized phase II trial. Stereotactic radiotherapy is one of the most frequently chosen treatment options for brain metastases. There are an increasing number of long term survivors. Brain necrosis (e.g. radio necrosis) is the most important long term side effect of the treatment, occurring in up to 40% of patients, dependent on the size of the metastasis and delivered radiotherapy dose. Retrospective studies have shown that the incidence of radio necrosis, as well as local tumor recurrence, can be decreased with a risk difference of around 20% by administrating fractionated stereotactic radiotherapy (fSRT, e.g. five fractions) over single fraction stereotactic radiotherapy, especially in large brain metastases. In this trial, one group is treated with SRT in one or three fractions. The other group is treated with fSRT in five fractions. Survival, toxicity and patient reported quality of life are monitored.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jaap D Zindler, MD, PhD; Phone Number: +31-88-9792013; Email: j.zindler@haaglandenmc.nl
• Study Contact Backup: Name: Mirjam Mast, PhD; Phone Number: +31-88-9792013; Email: m.mast@haaglandenmc.nl

Study Locations

• Netherlands
  • Zuid-Holland
    • Leidschendam, Zuid-Holland, Netherlands, 2262 BA
      • Recruiting
      • Haaglanden Medisch Centrum
      • Contact: Jaap Zindler, Dr; Email: j.zindler@haaglandenmc.nl
      • Contact: Ursula Fisscher, PhD; Email: u.fisscher@haaglandenmc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• At least one brain metastasis of large cell cancer suitable for SRT
• Karnofsky Performance Status ≥ 70
• Ability to provide written informed consent
• New brain metastases during follow-up after surgery allowed (when outside of resection cavity area)
• New brain metastases during follow-up after previous SRT allowed (when outside of previous irradiation field)

Exclusion Criteria:

• Contra-indication for MRI scan
• Primary tumor of small cell lung cancer, germinoma or lymphoma
• Prior whole brain radiotherapy or SRT on the current target brain metastases (in field re-irradiation)
• Presence of leptomeningeal metastases
• Previous inclusion in the SAFESTEREO study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SRT (stereotactic radiotherapy); stereotactic radiotherapy in 1 or 3 fractions of 8 Gy up to 15-24 Gy	Radiation: SRT; SRT
Experimental: fSRT (hypo fractionated stereotactic radiotherapy); hypo fractionated stereotactic radiotherapy in 5 fractions of 7 Gy up to 35 Gy. Brain stem metastases 5 fractions of 6 Gy up to 30 Gy	Radiation: fSRT; fSRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
radio necrosis or local failure	Incidence of either radio necrosis or local failure according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM).	2 years after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	median survival with Kaplan Meyer analysis	2 years after treatment
symptomatic radio necrosis (RN) or local failure (LF)	incidence of RN or LF within 2 years after SRT	2 years after treatment
salvage treatment	incidence of salvage treatment within 2 years after SRT	2 years after treatment
distant brain recurrences	incidence of distant brain recurrences within 2 years after SRT	2 years after treatment
Dose dexamethasone	Dose dexamethasone in mg per day	baseline - 2 years after treatment
Anti-epileptic drug use	Anti-epileptic drug use in mg per day	baseline - 2 years after treatment
Grade 2 or more toxicity (CTCAE v5.0)	incidence of Grade 2 or more toxicity according to CTCAE version 5.0 within 2 years after SRT	baseline - 2 years after treatment

Collaborators and Investigators

• Sponsor: Haaglanden Medical Centre
• Investigators: Principal Investigator: Jaap D Zindler, MD, PhD, Haaglanden MC

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: April 13, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: fractionated stereotactic radiotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: 2021-115LR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No