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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

Tracking Information
First Submitted Date  ICMJE May 23, 2019
First Posted Date  ICMJE June 3, 2019
Last Update Posted Date May 17, 2022
Actual Study Start Date  ICMJE October 15, 2019
Estimated Primary Completion Date October 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
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%
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
  • 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%
  • 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
  • Overall survival [ Time Frame: 2-years ]
    as defined from treatment start to death from any cause or last follow up
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: May 30, 2019)
  • 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
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE MRI - Guided Adaptive RadioTHerapy for Reducing XerostomiA in Head and Neck Cancer (MARTHA-trial)
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Head and Neck Cancer
  • Xerostomia Due to Radiotherapy
Intervention  ICMJE
  • 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
Study Arms  ICMJE 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
Interventions:
  • Other: Pre-defined MR-linac based IGRT and plan adaptation protocol
  • Diagnostic Test: salivary flow measurements
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 30, 2019)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 15, 2024
Estimated Primary Completion Date October 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Panagiotis Balermpas, M.D. +41 44 255 35 67 panagiotis.balermpas@usz.ch
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03972072
Other Study ID Numbers  ICMJE HN01_2019
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Panagiotis Balermpas, University of Zurich
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Panagiotis Balermpas
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Panagiotis Balermpas, M.D. University Hospital Zurich, Department of Radiation-Oncology
PRS Account University of Zurich
Verification Date May 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP