MRLinac Boost for Gynecological Cancers if Brachytherapy is Not Feasible (MARGARITA) (MARGARITA)

• ClinicalTrials.gov Identifier: NCT05937958
• Recruitment Status: Recruiting
• First Posted: July 10, 2023
• Last Update Posted: July 18, 2023
• Sponsor: UMC Utrecht
• Collaborator: Odense University Hospital
• Information provided by (Responsible Party): Astrid van Lier, UMC Utrecht

Study Description

Brief Summary:

The goal of this observational study is to explore the effectiveness and side effects of a high dose daily adapted SBRT (stereotactic body radiotherapy) boost delivered with MRLinac in patients with gynaecological cancers that cannot receive a brachytherapy boost to the primary tumour for different reasons (medical conditions, tumour extensions, etc). Current alternative for brachytherapy in these situations is often a non-adaptive conebeam- CT guided boost. Conebeam-CT guided non-adaptive high dose SBRT in under these circumstances is described being quite toxic.

The main questions this study aims to answer are:

• In how many cases could local control (i.e. total disappearance of the tumor) is be achieved with this treatment?
• Which side effects are observed in patients receiving this treatment?

Participants will be asked to fill out questionnaires (e.g. regarding side effects). Furthermore, participants are asked if their clinical data may be used for study purposes.

Condition or disease
Cervical Cancer; Gynecologic Cancer

Detailed Description:

Standard treatment of locally advanced cervical cancer is chemoradiotherapy (external beam radiotherapy (EBRT) and concomitant chemotherapy with weekly Cisplatin) followed by image guided brachytherapy (IGBT). Recently, the MR Linac has emerged as new option for delivering an external beam radiotherapy boost to the primary cervical tumour after (chemo)radiaton in case brachytherapy is not feasible. MR Linac in these cases can replace traditional EBRT boosts and allow for better visualisation of the anatomy, smaller treatment margins and online treatment planning adaptation. This comes with potential for higher dose to the target and less dose to the surrounding organs.

Like in IGBT, an MRL treatment provides the possibility to perform repetitive imaging before and even during each fraction and allows for dose adaptation to anatomical changes in individual patients. This way not not only the daily position of OARs in relation to the target can be taken into account, but also possible tumor regression which often is obtained during chemoradiation. Based on the experience collected so far, the MRL treatment may be an interesting treatment option in selected cases as daily MRI and plan adaptation leads to more confined dose distribution compared to CBCT-Linac options. However, dose levels for the MRL-boost are likely to be lower than for IGBT, therefore its effectiveness is still unsure.

Aims of the study:

• To introduce MRL-boost in locally advanced cervical cancer in a multicenter setting within the frame of a prospective observational study.
• To establish a bench-mark for clinical outcome with MRL-boost in a multi-center patient population with respect to local control, survival and toxicity.
• To establish reference material with regard to MRL-based DVH parameters; if applicable delineations according to the guidelines from the GEC-ESTRO gynecology working group will be used.
• To report image-based DVH parameters for target (GTV, CTV, PTV) and for OARs
• To report recurrence patterns
• To report Quality of Life

Type of design

This study is a multicenter prospective observational study. Patient registration and dosimetric reporting will be performed in the individual centers.

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: MRLinac Boost for Gynecological Cancers if Brachytherapy is Not Feasible
• Actual Study Start Date: April 1, 2023
• Estimated Primary Completion Date: October 1, 2025
• Estimated Study Completion Date: October 1, 2027

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :

1. Local control [ Time Frame: 3 months after MRLinac treatment ]
   Local control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
2. Local control [ Time Frame: 6 months after MRLinac treatment ]
   Local control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
3. Local control [ Time Frame: 12 months after MRLinac treatment ]
   Local control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
4. Local control [ Time Frame: 24 months after MRLinac treatment ]
   Local control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.

Secondary Outcome Measures :

1. Regional control [ Time Frame: 3 months after MRLinac treatment ]
   Regional control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
2. Regional control [ Time Frame: 6 months after MRLinac treatment ]
   Regional control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
3. Regional control [ Time Frame: 12 months after MRLinac treatment ]
   Regional control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
4. Regional control [ Time Frame: 24 months after MRLinac treatment ]
   Regional control of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care practices.
5. Distant failure [ Time Frame: 3 months after MRLinac treatment ]
   Distant failure of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care
6. Distant failure [ Time Frame: 12 months after MRLinac treatment ]
   Distant failure of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care
7. Distant failure [ Time Frame: 24 months after MRLinac treatment ]
   Distant failure of participating patients will be obtained from the hospital information systems. Patient follow-up is conducted to local standard of care
8. Gastrointestinal toxicity [ Time Frame: 3 months after MRLinac treatment ]
   Gastrointestinal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
9. Gastrointestinal toxicity [ Time Frame: 6 months after MRLinac treatment ]
   Gastrointestinal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
10. Gastrointestinal toxicity [ Time Frame: 24 months after MRLinac treatment ]
    Gastrointestinal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
11. Urogenital toxicity [ Time Frame: 3 months after MRLinac treatment ]
    Urogenital toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
12. Urogenital toxicity [ Time Frame: 6 months after MRLinac treatment ]
    Urogenital toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
13. Urogenital toxicity [ Time Frame: 24 months after MRLinac treatment ]
    Urogenital toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
14. Vaginal toxicity [ Time Frame: 3 months after MRLinac treatment ]
    Vaginal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
15. Vaginal toxicity [ Time Frame: 6 months after MRLinac treatment ]
    Vaginal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)
16. Vaginal toxicity [ Time Frame: 24 months after MRLinac treatment ]
    Vaginal toxicity of participating patients will be obtained from the hospital information systems. Toxicities are reported according to the Common Terminology Criteria for Adverse Events (CTCAE) dictionary. Patient recorded outcome is (tumor specific) questionaires. See MOMENTUM study (NCT04075305)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Patients with newly biopsy proven advanced stage gynecological cancers (excluding ovarian cancers) and endometrium in whom definitive (chemo)radiotherapy with curative intent is planned are qualified for the study, as well as, patients with recurrent gynecological cancers (excluding ovarian cancers) for which no prior (chemo)radiation was performed for which (chemo)radiotherapy with curative intent is planned.

Criteria

Inclusion Criteria:

• Patients with newly biopsy proven advanced stage gynecological cancers (excluding ovarian cancers) and endometrium in whom definitive (chemo)radiotherapy with curative intent is planned are qualified for the study, as well as, patients with recurrent gynecological cancers (excluding ovarian cancers) for which no prior (chemo)radiation was performed for which (chemo)radiotherapy with curative intent is planned.
• Patients with para-aortic metastatic nodes (stage IVB) to the level of L2 are also eligible but patients with further dissemination are not.
• Staging according to FIGO (2018, https://doi.org/10.1002/ijgo.12611) and TNM (version 9, 2021, https://doi.org/10.3322/caac.21663) staging.
• Patients who gave informed consent to take part in the MOMENTUM study (NCT04075305) to use their clinical data for publication and share their data with other (European) sites.

Exclusion Criteria:

• Hard contra-indication for MRI scanning

Contacts and Locations

Contacts

Contact: van Lier, PhD; +31 88 755 8800; a.l.h.m.w.vanlier@umcutrecht.nl

Locations

Denmark

Odense University Hospital; Recruiting

Odense, Denmark

Contact: Tine Schytte, PhD, MD

Netherlands

UMC Utrecht; Recruiting

Utrecht, Netherlands

Contact: Astrid van Lier, PhD + 31 88 755 8800 a.l.h.m.w.vanlier@umcutrecht.nl

Contact: Ina Schulz, PhD,MD +31 88 755 8800

Sub-Investigator: Femke van der Leij, PhD, MD

Sponsors and Collaborators

UMC Utrecht

Odense University Hospital

More Information

• Responsible Party: Astrid van Lier, Clinical Physicist, UMC Utrecht
• ClinicalTrials.gov Identifier: NCT05937958
• First Posted: July 10, 2023
• Last Update Posted: July 18, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: N/A yet

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astrid van Lier, UMC Utrecht:

Radiotherapy; MRLinac; Gynecologic Cancer; Local control; Toxicity; Cervical Cancer

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases