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Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases (MAESTRO)

Primary Purpose

Hepatic Metastasis

Status
Recruiting
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)
MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)
Sponsored by
University Hospital Heidelberg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Metastasis focused on measuring Magentic Resonance-guided Adaptive Stereotactic Body Radiotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Hospital of Heidelberg, Radiation OncologyRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

A

B

C

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Treatment related Toxicity
occurrence of treatment-related gastrointestinal or hepatobiliary CTCAE V5.0 toxicity of grade III or higher

Secondary Outcome Measures

Treatment related Toxicity
assesment of toxicity according to CTCAE V5.0 in all three treatment groups
Treatment related Quality of life
Changes in quality of life according to EORTC QLQ C-30
Treatment related Quality of life
Changes in quality of life according to EORTC QLQ LMC-21
local Tumor Control
Change of local Tumor size at one specific site
locoregional control
Change of local Tumor size within a defined local region
distant tumor control
apparence of distant Tumor leasions
progression-free survival (PFS)
time of suvival without Tumor progression
overall survival (OS)
time of Survival of studypopulation
Changes in applied biological effective doses (BED) to the target Volumen (Tumor)
BED increase and OAR doses with MRgSBRT compared to initial ITV-based planning in arms A and C
Evaluation of potential prognostic biomarkers
Changes in blood Levels of blood Parameters compared to reference samples

Full Information

First Posted
August 3, 2021
Last Updated
August 25, 2021
Sponsor
University Hospital Heidelberg
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1. Study Identification

Unique Protocol Identification Number
NCT05027711
Brief Title
Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases
Acronym
MAESTRO
Official Title
Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases - MAESTRO -
Study Type
Interventional

2. Study Status

Record Verification Date
August 2021
Overall Recruitment Status
Recruiting
Study Start Date
August 12, 2021 (Actual)
Primary Completion Date
January 31, 2024 (Anticipated)
Study Completion Date
January 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Heidelberg

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Metastasis
Keywords
Magentic Resonance-guided Adaptive Stereotactic Body Radiotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Magnetic Resonance-guided Stereotactic Body Radiotherapy (MRgSBRT), if a biologically effective dose (BED) of ≥ 100 Gy is achievable using an ITV
Arm Title
B
Arm Type
Experimental
Arm Description
ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT), if a biologically effective dose (BED) of ≥ 100 Gy is achievable using an ITV
Arm Title
C
Arm Type
Experimental
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)
Intervention Description
ITV (Internal target volume)-based Stereotactic Body Radiotherapy (ITV-SBRT)
Intervention Type
Radiation
Intervention Name(s)
MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)
Intervention Description
MRgSBRT (Magnetic Resonance-guided Stereotactic Body Radiotherapy)
Primary Outcome Measure Information:
Title
Treatment related Toxicity
Description
occurrence of treatment-related gastrointestinal or hepatobiliary CTCAE V5.0 toxicity of grade III or higher
Time Frame
within the first year after radiation treatment
Secondary Outcome Measure Information:
Title
Treatment related Toxicity
Description
assesment of toxicity according to CTCAE V5.0 in all three treatment groups
Time Frame
within 24 months after radiation treatment
Title
Treatment related Quality of life
Description
Changes in quality of life according to EORTC QLQ C-30
Time Frame
within 24 months after radiation treatment
Title
Treatment related Quality of life
Description
Changes in quality of life according to EORTC QLQ LMC-21
Time Frame
within 24 months after radiation treatment
Title
local Tumor Control
Description
Change of local Tumor size at one specific site
Time Frame
within 24 months after radiation treatment
Title
locoregional control
Description
Change of local Tumor size within a defined local region
Time Frame
within 24 months after radiation treatment
Title
distant tumor control
Description
apparence of distant Tumor leasions
Time Frame
within 24 months after radiation treatment
Title
progression-free survival (PFS)
Description
time of suvival without Tumor progression
Time Frame
24 months after radiation treatment
Title
overall survival (OS)
Description
time of Survival of studypopulation
Time Frame
24 months after radiation treatment
Title
Changes in applied biological effective doses (BED) to the target Volumen (Tumor)
Description
BED increase and OAR doses with MRgSBRT compared to initial ITV-based planning in arms A and C
Time Frame
through study completion, an average of 1 year
Title
Evaluation of potential prognostic biomarkers
Description
Changes in blood Levels of blood Parameters compared to reference samples
Time Frame
within 24 months after radiation treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Juliane Hörner-Rieber, PD
Phone
+496221 56
Ext
2802
Email
juliane.hörner-rieber@med.uni-heidelberg.de
First Name & Middle Initial & Last Name or Official Title & Degree
Philipp Hoegen, MD
Phone
+496221 56
Ext
2802
Email
philipp.hoegen@med.uni-heidelberg.de
Facility Information:
Facility Name
University Hospital of Heidelberg, Radiation Oncology
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jürrgen Debus, MD PHD

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35346270
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.
Results Reference
derived

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Magnetic Resonance-guided Adaptive Stereotactic Body Radiotherapy for Hepatic Metastases

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