Clinical trial NCT03972072: MRI - Guided Adaptive RadioTHerapy for Reducing XerostomiA in Head and Neck Cancer (MARTHA-trial)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Head and Neck Cancer
Xerostomia Due to Radiotherapy
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2019-06-03
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Percentage of patients with xerostomia of grade 2 or worse
timeFrame: 12 month-follow up
Secondary outcomes:
measure: Percentage of patients with xerostomia of grade 2 or worse
timeFrame: 6- and 24-months follow up
measure: Locoregional control rate as defined from treatment start to histologically confirmed tumor progression, persistence or last follow up
timeFrame: 2-years
measure: Overall survival
timeFrame: 2-years
measure: 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)
timeFrame: 6 months after treatment
measure: 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
timeFrame: 6 months after treatment
measure: 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)
timeFrame: 12 months after treatment
measure: 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
timeFrame: 12 months after treatment
measure: 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)
timeFrame: 24 months after treatment
measure: 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
timeFrame: 24 months after treatment
measure: Toxicity rates
timeFrame: weekly during radiotherapy and at 3, 6, 9, 12, 15, 18, 21 and 24 months
Other outcomes:
measure: variation of radiomics features (delta radiomics) of the parotid glands
timeFrame: 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)
measure: variation of tumor radiomics features (delta radiomics) for tumor control for the definitively irradiated (non-surgically treated) patients
timeFrame: 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)
measure: longitudinal inflammation profiling
timeFrame: Up to 3 months after enrollment (value assessment at baseline, after one week of treatment, last week of treatment and first follow up)
measure: longitudinal immune profiling
timeFrame: Up to 3 months after enrollment (value assessment at baseline, after one week of treatment and first follow up)
Locations:
city: Zurich
country: Switzerland
facility: Zurich University Hospital
Study officials:
affiliation: University Hospital Zurich, Department of Radiation-Oncology
name: Panagiotis Balermpas, M.D.
role: PRINCIPAL_INVESTIGATOR
References: