MRI - Guided Adaptive RadioTHerapy for Reducing XerostomiA in Head and Neck Cancer (MARTHA-trial) (MARTHA)

July 30, 2026 updated by: Panagiotis Balermpas

MARTHA-trial: MRI - Guided Adaptive RadioTHerapy for Reducing XerostomiA in Head and Neck Cancer Including Longitudinal Evaluation of the Patient's Immune Profile Under Radiotherapy

Radiotherapy is the main treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN). Many advances regarding tumor control and patient survival have been made over the past decades. However, treatment-induced toxicity remains a crucial problem, leading to reduced quality of life and permanent impairment for many survivors. Xerostomia is up to this day the leading cause of late toxicity for these patients. Toxicity has been reduced by implementation of modern image guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT), but the low soft-tissue contrast of routine x-ray image guidance does not allow exact planning adaptation and daily imaging is associated with high radiation exposure. Furthermore, despite the routinely use of IMRT, rates of clinically relevant xerostomia (i.e. grade 2 or worse) are still common and reported in approximately 38%. Recently developed hybrid machines (MRidian®-CE approval since 2016), consisting of a linear accelerator and an integrated low-field MRI, could allow a) better visualization of tumor and organs at risk, such as parotid glands during patient positioning and daily treatment, b) daily imaging without additional radiation exposure, c) narrowest established safety margins for the treatment volumes, and finally d) repetitive adaptation of target volumes according to changes in patient weight and tumor anatomy during the radiotherapy course. These procedures would facilitate a high-precision treatment and help reduce dose exposure of critical structures.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
49

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Switzerland
      • Zurich, Switzerland, 8091
        • Zurich University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically proven squamous cell carcinoma of the oral cavity oro- or hypopharynx or larynx, Stages II-IVB, requiring definitive or postoperative bilateral neck irradiation
  • Age ≥ 18 years, no upper age limit
  • ECOG-Performance score < 2
  • The trial is open to both genders
  • History/physical examination within 30 days prior to registration by head and neck surgeon and Radiation Oncologist
  • FDG-PET-CT-scan within 30 days prior to registration

Exclusion Criteria:

  • Not adequately controlled hepatitis or HIV disease (HIV-viral load detectable)
  • Second non-controlled malignancy other than basalioma or cervical/genital/anal in situ neoplasia during the last 2 years before enrollment
  • Bilirubin > 2,0 mg/dl, SGOT, SGPT, AP, Gamma-GT >3x norm, GFR < 30 ml/min
  • leucocytes <3,5 x 10^9/l or platelets < 100 x 10^9/l or neutrophiles < 1,5 x 10^9/l
  • Other severe comorbidities or psychic disorders (e.g. myocardial infraction within 6 months prior to registration, permanent cardiac arrhythmia, COPD Gold IV, hepatitis B/C, schizophrenia, ongoing alcohol abuse etc.)
  • Lactating and pregnant women
  • Previous radiotherapy of the neck
  • Contraindications for MRI (e.g. pacemaker/ICD, tattoos, cochlear or other not MR-compatible implants)
  • Pre-existing salivary gland disease (e.g. Sjorgen's-syndrome) or xerostomia-inducing medication (e.g. anticholinergic medication like tricyclic antidepressant)
  • Claustrophobia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Single Intervention Arm
daily imaging for MR-IGRT once weekly offline plan adaptation subjective/objective LENT-SOMA xerostomia-evaluation including flow measurements at baseline, 6 month-, 12 month- and 24 month-follow up EORTC-QoL questionnaires at baseline, 6 month-, 12 month- and 24 month-follow up
Other: Pre-defined MR-linac based IGRT and plan adaptation protocol
daily MR-imaging/MR guided radiotherapy once weekly offline plan adaptation to a total of 6
Diagnostic test: salivary flow measurements
baseline, 6 month-, 12 month- and 24 month-follow up salivary flow measurements and LENT-SOMA subjective/objective evaluation of xerostomia

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of patients with xerostomia of grade 2 or worse
Time Frame: 12 month-follow up
will be evaluated by the LENT-SOMA (Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA)) side-effect scale: SOM (1)-(4) (higher score represents higher grade xerostomia), A: objective flow measurement (1) 76-95%, (2) 51-75%, (3) 26-50%, (4) 0-25%
12 month-follow up

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of patients with xerostomia of grade 2 or worse
Time Frame: 6- and 24-months follow up
will be evaluated by the LENT-SOMA (Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA)) side-effect scale: SOM (1)-(4) (higher score represents higher grade xerostomia), A: objective flow measurement (1) 76-95%, (2) 51-75%, (3) 26-50%, (4) 0-25%
6- and 24-months follow up
Locoregional control rate as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up
Time Frame: 2-years
as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up
2-years
Overall survival
Time Frame: 2-years
as defined from treatment start to death from any cause or last follow up
2-years
Description of Quality of life - scoring 6 months after treatment, assessed according to the general EORTC-quality of life "core" questionnaire QLQ C30 (overall quality of life for cancer patients)
Time Frame: 6 months after treatment

Questionnaire consists of 30 questions with a maximal score of 100. Absolute scores after linear transformation will be reported as descriptive statistics The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

See also: https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf
6 months after treatment
Description of Head-Neck cancer related symptoms 6 months after treatment, assessed according to the specific EORT-head and neck quality of life supplementary questionnaire HN35
Time Frame: 6 months after treatment
total scoring of an additional 35 questions with a similar approach to that of the core questionnaire will be reported as descriptive statistics
6 months after treatment
Description of Quality of life - scoring 12 months after treatment, assessed according to the general EORTC-quality of life "core" questionnaire QLQ C30 (overall quality of life for cancer patients)
Time Frame: 12 months after treatment

Questionnaire consists of 30 questions with a maximal score of 100. Absolute scores after linear transformation will be reported as descriptive statistics The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

See also: https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf
12 months after treatment
Description of Head-Neck related symptoms 12 months after treatment, assessed according to the specific EORT-head and neck quality of life supplementary questionnaire HN35
Time Frame: 12 months after treatment
total scoring of an additional 35 questions with a similar approach to that of the core questionnaire will be reported as descriptive statistics
12 months after treatment
Description of Quality of life - scoring 24 months after treatment, assessed according to the general EORTC-quality of life "core" questionnaire QLQ C30 (overall quality of life for cancer patients)
Time Frame: 24 months after treatment

Questionnaire consists of 30 questions with a maximal score of 100. Absolute scores after linear transformation will be reported as descriptive statistics The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

A high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.

See also: https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf
24 months after treatment
Description of Head-Neck related symptoms 24 months after treatment, assessed according to the specific EORT-head and neck quality of life supplementary questionnaire HN35
Time Frame: 24 months after treatment
total scoring of an additional 35 questions with a similar approach to that of the core questionnaire will be reported as descriptive statistics
24 months after treatment
Toxicity rates
Time Frame: weekly during radiotherapy and at 3, 6, 9, 12, 15, 18, 21 and 24 months
evaluated by the CTCAE v5-questionnaires
weekly during radiotherapy and at 3, 6, 9, 12, 15, 18, 21 and 24 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
variation of radiomics features (delta radiomics) of the parotid glands
Time Frame: Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)
as assessed by serial T1/T2 images acquired with the hybrid 0.35 T MR-linac and correlated with xerostomia at 12 months
Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)
variation of tumor radiomics features (delta radiomics) for tumor control for the definitively irradiated (non-surgically treated) patients
Time Frame: Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)
as assessed by serial T1/T2 images acquired with the hybrid 0.35 T MR-linac and correlated with tumor control at 24 months
Up to 9 weeks after enrollment: Images acquired at baseline (i.e. up to 10 days before first radiotherapy fraction, used for radiotherapy planning) and daily radiotherapy treatment (treatment days 1-35, 7 weeks)
longitudinal inflammation profiling
Time Frame: Up to 3 months after enrollment (value assessment at baseline, after one week of treatment, last week of treatment and first follow up)
Prognostic value of inflammation surrogates (neutrophile count, CRP/ albumin ratio) in the peripheral blood
Up to 3 months after enrollment (value assessment at baseline, after one week of treatment, last week of treatment and first follow up)
longitudinal immune profiling
Time Frame: Up to 3 months after enrollment (value assessment at baseline, after one week of treatment and first follow up)
Prognostic value of different circulating (at different time-points) immune cells as defined by longitudinal FACS-analysis of immune phenotype in the peripheral blood
Up to 3 months after enrollment (value assessment at baseline, after one week of treatment and first follow up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Panagiotis Balermpas

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Panagiotis Balermpas, M.D., University Hospital Zurich, Department of Radiation-Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 15, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 21, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 24, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 30, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 3, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HN01_2019

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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