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

Head and Neck Cancer Clinical Trial

— MARTHA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03972072
• Other study ID #: HN01_2019
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2019
• Est. completion date: March 15, 2026

Study information

• Verified date: November 2023
• Source: University of Zurich
• Contact: Panagiotis Balermpas, M.D.
• Phone: +41 44 255 35 67
• Email: panagiotis.balermpas[@]usz.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: March 15, 2026
• Est. primary completion date: March 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Xerostomia
• Xerostomia Due to Radiotherapy

Intervention

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

Locations

Country	Name	City	State
Switzerland	Zurich University Hospital	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Panagiotis Balermpas

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	variation of radiomics features (delta radiomics) of the parotid glands	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)
Other	variation of tumor radiomics features (delta radiomics) for tumor control for the definitively irradiated (non-surgically treated) patients	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)
Other	longitudinal inflammation profiling	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)
Other	longitudinal immune profiling	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)
Primary	Percentage of patients with xerostomia of grade 2 or worse	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	Percentage of patients with xerostomia of grade 2 or worse	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
Secondary	Locoregional control rate as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up	as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up	2-years
Secondary	Overall survival	as defined from treatment start to death from any cause or last follow up	2-years
Secondary	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)	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
Secondary	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	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
Secondary	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)	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
Secondary	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	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
Secondary	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)	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
Secondary	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	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
Secondary	Toxicity rates	evaluated by the CTCAE v5-questionnaires	weekly during radiotherapy and at 3, 6, 9, 12, 15, 18, 21 and 24 months