Hypofractionated Versus Single Fraction Stereotactic Adjuvant Radiotherapy to the Resection Cavity of Brain Metastases

Brain Metastases Clinical Trial

— SATURNUS  

Official title:

Hypofractionated Stereotactic Radiotherapy Versus Single Fraction Stereotactic Radiosurgery to the Resection Cavity of Brain Metastases After Surgical Resection - A Prospective, Randomized, Controlled, Monocentric Phase III Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05160818
• Other study ID #: RadOnc MRI TUM - 2
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2021
• Est. completion date: August 1, 2025

Study information

• Verified date: December 2021
• Source: Technische Universität München
• Contact: Maria Waltenberger
• Phone: +49-89-4140-8281
• Email: maria.waltenberger[@]mri.tum.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This prospective, randomized, controlled, monocentric clinical phase III study focuses on stereotactic irradiation of resection cavities of brain metastases after surgical resection and seeks to demonstrate the superiority of fractionated irradiation schemes in terms of local control.

Description:

There is a growing scientific focus on single fraction stereotactic (SRS) and hypofractionated stereotactic irradiation (HFSRT) after surgical resection of brain metastasis and its use is more frequently recommended in international guidelines. Despite intensive research, the optimal fractionation scheme and dose prescription for adjuvant irradiation of the resection cavity remains unclear.

Based on our own institutional data [Cit.1] and a recently published metaanalysis [Cit.2], we hypothesize that local control (LC) after HFSRT is superior compared to SRS in terms of LC. To evaluate the hypothesis in a prospective, randomized, controlled setting we designed the SATURNUS study.

A total of 126 patients will be randomized 1:1 to either HFSRT (dose 6-7 x 5 Gy) or SRS (dose 1 x 12-20 Gy). If further unresected brain metastases are present, they will be treated with SRS (1 x 14 - 22 Gy). Irradiation is carried out with a Gamma Knife or a Linear Accelerator. In line with current clinical practice, the choice of positioning method for SRS with the Gamma Knife (mask or stereotactic frame) is left to the patient. In the case of SRS with the Linear Accelerator or HFSRT, fixation is done with a mask as technically not otherwise feasible. Follow-up-MRI will be at least carried out 6 weeks and 3, 6, 9 and 12 months after treatment. Primary endpoint of the study is local control (LC) at the irradiated resection cavity after 12 months. Locoregional control (LRC) and overall survival (OS) as well as salvage-treatments, irradiation-associated toxicities (especially rate of radionecrosis) and quality-of-life parameters are investigated as secondary endpoints.

To the best of our knowledge, the SATURNUS study is the only randomized phase III study comparing different techniques of postoperative stereotactic radiotherapy after resection of brain metastases adequately powered to detect a superiority of HSFRT regarding LC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 126
• Est. completion date: August 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed solid tumor disease

• One to three resected brain metastases

• Consent to perform adjuvant irradiation by an interdisciplinary tumor board

• Completed wound healing

• Resection within the last six weeks at the time of study inclusion

• Diameter of the resection cavity = 4 cm (on Planning MRI)

• Age > 18 years

• KPS > 60%

• Adequate contraceptive measures for fertile women / men

• Written informed consent (must be available before enrolment in the trial)

Exclusion Criteria:

• Contraindication for repetitive contrast enhanced MRI

• Leptomeningeal disease

• Small cell histology, hematological malignancies and / or germ cell malignancies

• Previous irradiation of the brain

• Pregnant and lactating women

• Inability to understand the character and consequences of the study

• Withdrawal of consent

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Resection Cavity

Intervention

Radiation:
• Hypofractionated stereotactic radiotherapy (HFSRT) versus single fraction stereotactic radiotherapy radiosurgery (SRS)
intervention description see above

Locations

Country	Name	City	State
Germany	Dept. Radiation Oncology	Munich	Bavaria

Sponsors (1)

Lead Sponsor	Collaborator
Technische Universität München

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Akanda ZZ, Hong W, Nahavandi S, Haghighi N, Phillips C, Kok DL. Post-operative stereotactic radiosurgery following excision of brain metastases: A systematic review and meta-analysis. Radiother Oncol. 2020 Jan;142:27-35. doi: 10.1016/j.radonc.2019.08.024. Epub 2019 Sep 25. — View Citation

Specht HM, Kessel KA, Oechsner M, Meyer B, Zimmer C, Combs SE. HFSRT of the resection cavity in patients with brain metastases. Strahlenther Onkol. 2016 Jun;192(6):368-76. doi: 10.1007/s00066-016-0955-2. Epub 2016 Mar 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Local control	Local control at the resected site(s)	12 months after adjuvant radiotherapy
Secondary	LC	Local control at all treated site(s)	12 months after adjuvant radiotherapy
Secondary	LRC	Locoregional control=CNS progression free survival	12 months after adjuvant radiotherapy
Secondary	OS	Overall survival	12 months after adjuvant radiotherapy
Secondary	Salvage-free survival	Overall survival	12 months after adjuvant radiotherapy
Secondary	Intracranial salvage therapy	Number and kind of intracranial salvage treatments	12 months after adjuvant radiotherapy
Secondary	Pseudoprogression	Rate of pseudoprogression	up to 12 months after adjuvant radiotherapy
Secondary	Irradiation-related toxicity	according to CTCAE v4.03, especially rate of radionecrosis	up to 12 months after adjuvant radiotherapy
Secondary	QoL	Quality of life according to EORTC QLQ-C30 and EORTC QLQ-B20	up to 12 months after adjuvant radiotherapy
Secondary	Time to loss of independence	defined as decrease in Barthel index by > 20 points	up to 12 months after adjuvant radiotherapy