Ignite Creation Date:
2025-12-25 @ 4:04 AM
Ignite Modification Date:
2025-12-26 @ 3:00 AM
Study NCT ID:
NCT07253402
Status:
RECRUITING
Last Update Posted:
2025-11-28
First Post:
2025-11-19
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Microbiota-guided Radiotherapy for Head and Neck Cancer
Sponsor:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Organization:
Study Overview
Official Title:
MIcrobiota-Guided RAdiotherapy for Head and Neck Cancer. (MIGRHAN)
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MIGRAHN
Brief Summary:
Head and neck cancer (HNC) is the sixth most common cancer worldwide. Therapeutic outcomes for HNC remain unsatisfactory and heterogeneous, with 5-year survival rates ranging from 28% to 67% overall. Moreover, HNC patients experience side effects during treatment, including inflammation and ulceration of the oral mucosa caused by radiation or cytotoxic agents (oral mucositis), which represents a limiting factor for both the escalation of radiotherapy dosage and the duration of treatment.
Several observational studies have highlighted statistical associations between the oral microbiota and numerous factors related to HNC and its therapeutic course. The working hypothesis of this study is that it is possible to establish causal relationships between the functional traits of the human oral microbiota and the effectiveness of radiotherapy in HNC treatment, directly from the analysis of data collected in observational cohorts, by leveraging the statistical framework of causal inference.
The oral microbiota of HNC patients enrolled in the study will be characterised through metagenomic sequencing of saliva samples collected from each patient, at radiotherapy-baseline, at 2 weeks from radiotherapy start and at radiotherapy end.
Main Objectives of the Study:
* Creation of a dataset of the oral microbiota in HNC patients, including both bacterial and viral components, as well as data linked to treatment effectiveness and side effects.
* Estimation of the causal effect of the functional traits of the oral microbiota on the modulation of radiotherapy in HNC.
* Development of predictive models for local tumour control and for oral mucositis, based on the oral microbiota of HNC patients.
Clinical Relevance:
The causal relationships inferred between the functional/metabolic traits of the microbiota and radiotherapy effectiveness will help build interpretable predictive models and reveal strategies to reprogram the microbiota functionality of patients with head and neck cancer. This will increase the likelihood of tumour eradication or control while reducing the risk of radiation-induced side effects.
Several observational studies have highlighted statistical associations between the oral microbiota and numerous factors related to HNC and its therapeutic course. The working hypothesis of this study is that it is possible to establish causal relationships between the functional traits of the human oral microbiota and the effectiveness of radiotherapy in HNC treatment, directly from the analysis of data collected in observational cohorts, by leveraging the statistical framework of causal inference.
The oral microbiota of HNC patients enrolled in the study will be characterised through metagenomic sequencing of saliva samples collected from each patient, at radiotherapy-baseline, at 2 weeks from radiotherapy start and at radiotherapy end.
Main Objectives of the Study:
* Creation of a dataset of the oral microbiota in HNC patients, including both bacterial and viral components, as well as data linked to treatment effectiveness and side effects.
* Estimation of the causal effect of the functional traits of the oral microbiota on the modulation of radiotherapy in HNC.
* Development of predictive models for local tumour control and for oral mucositis, based on the oral microbiota of HNC patients.
Clinical Relevance:
The causal relationships inferred between the functional/metabolic traits of the microbiota and radiotherapy effectiveness will help build interpretable predictive models and reveal strategies to reprogram the microbiota functionality of patients with head and neck cancer. This will increase the likelihood of tumour eradication or control while reducing the risk of radiation-induced side effects.
Detailed Description:
The research question addressed by this study is the need to bridge the current gap in understanding the role of the microbiota, as well as potential microbiota-targeted therapies such as antibiotic use, in the treatment of head and neck cancer (HNC). The working hypothesis is that causal relationships can be established between the functional traits of the human oral microbiota and the effectiveness of radiotherapy for HNC, using the statistical framework of causal inference. Identifying this causal knowledge is essential to design and implement microbiota-guided radiotherapy, where the patient's oral microbiota is profiled prior to treatment and evaluated against the risk of developing oral mucositis and/or experiencing unfavorable outcomes. From a microbiota-based perspective, assessing whether different radiotherapy plans may result in tolerable or intolerable side effects would be crucial for developing personalized radiotherapy programs that could enhance tumor control. Furthermore, since this study involves functional metagenomic analysis of the microbiota, it will be possible to infer the mechanisms through which the microbiota modulates radiotherapy and to exploit these insights for the design of new microbiota-based clinical strategies. Such strategies may include administration of specific nutritional supplements, antibiotics, or probiotics to optimise therapy tolerance and improve treatment outcomes.
Study design and setting: MIGRHAN is a single-institution, prospective observational cohort study with an expected total duration of approximately six years. At least 96 consecutive patients with head and neck cancer referred for curative radiotherapy will be enrolled over a 36-month period. Their treatment, toxicity monitoring, and follow-up (3 years) will follow routine clinical practice in accordance with national and international guidelines. Recruitment will take place exclusively at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, with patient enrollment starting in September 2025 and planned completion by October 2031.
Study workflow: Before enrollment, patients will provide written informed consent. Baseline assessments (from -28 days to treatment start) will include demographic data, medical history, dental evaluation, clinical examination, laboratory tests (blood tests, urinalysis, thyroid function, coagulation), radiological imaging (CT scan, multiparametric MRI, whole body FDG-PET/CT or bone scan), and collection of a saliva sample for microbiota profiling. During radiotherapy, weekly clinical evaluations, toxicity assessments following CTCAE v5.0, and patient questionnaires will be conducted, alongside repeated laboratory analyses and collection of dosimetric treatment data (DICOM-RT). At the end of radiotherapy and during follow-up visits (3, 6, and 12 months), patients will undergo repeat clinical evaluations, imaging (MRI, CT, PET/CT or bone scan as indicated), laboratory tests, and additional saliva collections. Long-term follow-up will include survival assessment up to three years post-treatment.
Study design and setting: MIGRHAN is a single-institution, prospective observational cohort study with an expected total duration of approximately six years. At least 96 consecutive patients with head and neck cancer referred for curative radiotherapy will be enrolled over a 36-month period. Their treatment, toxicity monitoring, and follow-up (3 years) will follow routine clinical practice in accordance with national and international guidelines. Recruitment will take place exclusively at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, with patient enrollment starting in September 2025 and planned completion by October 2031.
Study workflow: Before enrollment, patients will provide written informed consent. Baseline assessments (from -28 days to treatment start) will include demographic data, medical history, dental evaluation, clinical examination, laboratory tests (blood tests, urinalysis, thyroid function, coagulation), radiological imaging (CT scan, multiparametric MRI, whole body FDG-PET/CT or bone scan), and collection of a saliva sample for microbiota profiling. During radiotherapy, weekly clinical evaluations, toxicity assessments following CTCAE v5.0, and patient questionnaires will be conducted, alongside repeated laboratory analyses and collection of dosimetric treatment data (DICOM-RT). At the end of radiotherapy and during follow-up visits (3, 6, and 12 months), patients will undergo repeat clinical evaluations, imaging (MRI, CT, PET/CT or bone scan as indicated), laboratory tests, and additional saliva collections. Long-term follow-up will include survival assessment up to three years post-treatment.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: