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

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ClinicalTrials.gov Identifier: NCT03972072
Recruitment Status : Recruiting
First Posted : June 3, 2019
Last Update Posted : May 17, 2022
Sponsor:
Information provided by (Responsible Party):
Panagiotis Balermpas, University of Zurich

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Head and Neck Cancer Xerostomia Due to Radiotherapy Other: Pre-defined MR-linac based IGRT and plan adaptation protocol Diagnostic Test: salivary flow measurements Not Applicable

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 44 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : October 15, 2019
Estimated Primary Completion Date : October 15, 2023
Estimated Study Completion Date : October 15, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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 Outcome Measures:
  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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03972072


Contacts
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Contact: Panagiotis Balermpas, M.D. +41 44 255 35 67 panagiotis.balermpas@usz.ch

Locations
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Switzerland
Zurich University Hospital Recruiting
Zurich, Switzerland, 8091
Contact: Panagiotis Balermpas, M.D.    +41797493375    rao_akademischesoffice@usz.ch   
Contact: Debra Fesslmeier    +41432530151    rao_akademischesoffice@usz.ch   
Sponsors and Collaborators
Panagiotis Balermpas
Investigators
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Principal Investigator: Panagiotis Balermpas, M.D. University Hospital Zurich, Department of Radiation-Oncology
More Information
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Responsible Party: Panagiotis Balermpas, Sponsor-Investigator, Senior Consultant, University of Zurich
ClinicalTrials.gov Identifier: NCT03972072    
Other Study ID Numbers: HN01_2019
First Posted: June 3, 2019    Key Record Dates
Last Update Posted: May 17, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Head and Neck Neoplasms
Xerostomia
Neoplasms by Site
Neoplasms
 Salivary Gland Diseases
Mouth Diseases
Stomatognathic Diseases