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NCT Number: NCT03972072

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Head and Neck Cancer Head and Neck Neoplasms Neoplasms Neoplasms by Site Xerostomia Due to Radiotherapy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Zurich University Hospital

Zurich, 8091, Switzerland

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Pre-defined MR-linac based IGRT and plan adaptation protocol

Other

daily MR-imaging/MR guided radiotherapy once weekly offline plan adaptation to a total of 6

salivary flow measurements

Diagnostic Test

baseline, 6 month-, 12 month- and 24 month-follow up salivary flow measurements and LENT-SOMA subjective/objective evaluation of xerostomia

Primary outcomes

  1. 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%

Secondary outcomes

  1. 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%

  2. 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

  3. Overall survival

    Time frame: 2-years

    as defined from treatment start to death from any cause or last follow up

  4. 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

  5. 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. 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

  7. 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

  8. 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

  9. 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

  10. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  4. 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

Sponsors and collaborators

Lead sponsor

Panagiotis Balermpas

Other

Registry information

Official study title

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

Acronym: MARTHA

Important dates

Study start
2019
Primary completion
2025
Study completion
2026
First posted
Jun 3, 2019
Registry last updated
Apr 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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