Clinical trial NCT05027711: Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases
Official title: Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases - MAESTRO -
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hepatic Metastasis
Keywords: Magentic Resonance-guided Adaptive Stereotactic Body Radiotherapy
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2021-08-30
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Treatment related Toxicity
timeFrame: within the first year after radiation treatment
Secondary outcomes:
measure: Treatment related Toxicity
timeFrame: within 24 months after radiation treatment
measure: Treatment related Quality of life
timeFrame: within 24 months after radiation treatment
measure: Treatment related Quality of life
timeFrame: within 24 months after radiation treatment
measure: local Tumor Control
timeFrame: within 24 months after radiation treatment
measure: locoregional control
timeFrame: within 24 months after radiation treatment
measure: distant tumor control
timeFrame: within 24 months after radiation treatment
measure: progression-free survival (PFS)
timeFrame: 24 months after radiation treatment
measure: overall survival (OS)
timeFrame: 24 months after radiation treatment
measure: Changes in applied biological effective doses (BED) to the target Volumen (Tumor)
timeFrame: through study completion, an average of 1 year
measure: Evaluation of potential prognostic biomarkers
timeFrame: within 24 months after radiation treatment
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital of Heidelberg, Radiation Oncology
Study officials:
References:
citation: 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.