Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases

NCT ID: NCT05027711

Last Updated: 2024-01-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-12
• Study Completion Date: 2027-01-31

Brief Summary

Stereotactic body radiotherapy (SBRT) is an established local treatment method for patients with hepatic oligometastases. Liver metastases often occur in close proximity to radiosensitive organs at risk (OARs). This limits the possibility to apply sufficiently high doses needed for optimal local control. MR-guided radiotherapy (MRgRT) is expected to hold potential to improve hepatic SBRT by offering superior soft-tissue contrast for enhanced target identification as well as the benefit of daily real-time adaptive treatment. The MAESTRO trial therefore aims to assess the potential advantages of adaptive, gated MR-guided SBRT (MRgSBRT) compared to conventional SBRT at a standard linac using an ITV (internal target volume) approach (ITV-SBRT).

Detailed Description

Hepatic SBRT is a well-established local treatment method for technically or medically inoperable hepatic metastases. However, clinicians are often restricted in the utilization of hepatic SBRT due to dose limitations of the uninvolved liver and nearby OARs (e.g. small bowel, stomach, kidney). MR-guided radiotherapy with its superior soft-tissue contrast is believed to facilitate the precise detection of tumor position and interfractional changes in patient anatomy. Respiratory gating at the MR-Linac enables real-time visualization of the tumor as well as synchronization of beam delivery to the patient's breathing . Therefore, safety margins and thus the irradiated volume can possibly be decreased with MRgSBRT in comparison to ITV-based SBRT, reducing the risk of treatment-associated toxicity. Hepatic MRgSBRT of smaller target volumes might further offer the possibility of dose escalation for increasing local control. To our knowledge, only two retrospective analyses including 26 and 29 patients as well as one case report about hepatic MR-guided SBRT using a MR-Linac can be found in literature. As MR-guided adaptive SBRT is very staff intense and time consuming compared to standard ITV-based SBRT, prospective studies are needed to demonstrate the expected benefits of MR-guided adaptive SBRT. This trial will be conducted as a prospective, randomized, three-armed phase II study in 82 patients with hepatic metastases (solid malignant tumor, 1-3 hepatic metastases confirmed by magnetic resonance imaging (MRI), maximum diameter of each metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12cm), age ≥ 18 years, Karnofsky Performance Score ≥ 60%). If a biologically effective dose (BED) ≥ 100 Gy is feasible based on ITV-based planning, patients will be randomized to either MRgSBRT (Arm A) or ITV-based SBRT (Arm B). If a lesion cannot be treated with a BED ≥ 100 Gy, the patient will be treated in Arm C with MRgSBRT at the highest possible dose.

Conditions

Hepatic Metastasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

Magnetic Resonance-guided Stereotactic Body Radiotherapy (MRgSBRT), if a biologically effective dose (BED) of ≥ 100 Gy is achievable using an ITV

Group Type: EXPERIMENTAL

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

Intervention Type: RADIATION

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

B

ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT), if a biologically effective dose (BED) of ≥ 100 Gy is achievable using an ITV

Group Type: EXPERIMENTAL

ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)

Intervention Type: RADIATION

ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)

C

Magnetic Resonance-guided Stereotactic Body Radiotherapy (MRgSBRT). If a BED of ≥ 100 Gy cannot be achieved using an ITV concept (e.g. due to OAR constraints), patients will be treated in arm C using MRgSBRT with the highest achievable dose as deemed appropriate by the treating radiation oncologist

Group Type: EXPERIMENTAL

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

Intervention Type: RADIATION

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

Interventions

ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)

ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)

Intervention Type: RADIATION

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• confirmed underlying solid malignant tumor (no germ cell tumor, leukemia, lymphoma)
• 1-3 hepatic metastases confirmed by pre-therapeutic MRI
• indication for SBRT of 1-3 hepatic metastases
• maximum diameter each hepatic metastasis ≤ 5 cm (in case of 3 metastases: sum of diameters ≤ 12 cm)
• age ≥ 18 years of age
• Karnofsky Performance Score ≥ 60%
• ability to lie still on the radiotherapy treatment couch for at least one hour
• ability to hold one's breath for more than 25 seconds
• for women with childbearing potential, adequate contraception
• ability of subject to understand character and individual consequences of the clinical trial
• written informed consent (must be available before enrolment in the trial)

Exclusion Criteria

• refusal of the patients to take part in the study
• patients with primary liver cancer (eg. HCC, CCC)
• patients after liver transplantation
• impairment of liver function to an extent contraindicating radiotherapy (to the discretion of the treating radiation oncologist)
• active acute hepatic/biliary infection (e.g. hepatitis, cholangitis, cholecystitis)
• previous radiotherapy of the hepatobiliary system, if previous and current target volumes overlap MAESTRO Study Studienprotokoll Seite 25 von 54 Version 1.0 vom 17.12.2020
• patients who have not yet recovered from acute toxicities of prior therapies
• claustrophobia
• pregnant or lactating women
• contraindications against performing contrast-enhanced MRI scans (pacemakers, other implants making MRI impossible, allergy to gadolinium (GD)-based contrast agent)
• participation in another competing clinical study or observation period of competing trials

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Juergen Debus

Department Head

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University Hospital of Heidelberg, Radiation Oncology

Heidelberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Juliane Hörner-Rieber, PD

Role: CONTACT

juliane.hörner-rieber@med.uni-heidelberg.de

+496221 56 ext. 2802

Philipp Hoegen, MD

Role: CONTACT

philipp.hoegen@med.uni-heidelberg.de

+496221 56 ext. 2802

References

Hoegen P, Zhang KS, Tonndorf-Martini E, Weykamp F, Regnery S, Naumann P, Lang K, Ristau J, Korber SA, Dreher C, Buchele C, Rippke C, Renkamp CK, Paul KM, Konig L, Busch C, Krisam J, Sedlaczek O, Schlemmer HP, Niyazi M, Corradini S, Debus J, Kluter S, Horner-Rieber J. MR-guided adaptive versus ITV-based stereotactic body radiotherapy for hepatic metastases (MAESTRO): a randomized controlled phase II trial. Radiat Oncol. 2022 Mar 27;17(1):59. doi: 10.1186/s13014-022-02033-2.

Reference Type: DERIVED

PMID: 35346270 (View on PubMed)

Other Identifiers

RADONK-MAESTRO-2020

Identifier Type: -

Identifier Source: org_study_id