Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck

Study Overview
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Brief Summary
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DART is an exploratory molecular analysis study to assess potential early biomarkers of treatment response in squamous cell carcinoma of the head and neck (HNSCC)

Detailed Description
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If cancer that starts in the head or neck is not suitable for surgery or radiotherapy, then it cannot be cured. Unfortunately, people in this situation have a short life expectancy, with half dying within 12 months. There are treatments available that have helped people in this situation live longer, most recently drugs that stimulate the body's own immune system to attack the cancer, known as 'immunotherapy'. Some people do very well on these treatments, living many years, while the same treatments offer no benefit to others - it is not known why. This study is looking at collecting samples of a person's cancer, along with other body fluids, particularly blood and saliva, to see if the investigators can track changes in blood and saliva that happen in a person's cancer while they are receiving treatment. Additionally, samples of the cancer will be used to see if they can be grown in the laboratory to test growth behaviour and how well different treatments work. The investigators will ask people being treated for incurable cancer that started in the head and neck for permission to collect their blood and saliva, along with samples of their cancer tissue, while they are having treatment. Nearly all patients will require a sample of their cancer tissue taken with a needle (a 'biopsy') anyway, and tissue samples can be taken as part of this process. Similarly, the safe administration of cancer drugs requires blood tests before every course of treatment, and research bloods can be taken from the same blood draw. A small number of people will be asked whether they give their permission for an extra biopsy of their cancer to allow further comparisons in the laboratory.

Official Title
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Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Genetic: Circulating tumour DNA dynamics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older Patients with histologically confirmed cancer of the head and neck with evidence of recurrent or locally advanced cancer not suitable for treatment with curative intent, or metastatic disease. Receiving immunotherapy Ability to give informed consent for biological sample collection. Exclusion Criteria: Unable to undergo serial sample collection Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients receiving systemic therapies for cancers of the head and neck<br>Patients undergoing systemic therapy for recurrent, metastatic, or locally advanced cancer of the head and neck not suitable for treatment with curative intent. A biological research study involving the collection of blood, tumour tissue, saliva, and other body fluids routinely examined during cancer care (e.g. cerebrospinal fluid (CSF), ascites, urine, stool or pleural fluids). | Genetic: Circulating tumour DNA dynamics<br>* Circulating tumour DNA (ctDNA) can be identified in patients with a wide variety of cancers and has been shown to allow early prediction of disease relapse after treatment with curative intent in HNSCC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The level of circulating tumour DNA pre-treatment will be descriptively compared to the levels detected at subsequent time points |  | Through study completion, expected duration of 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To collect longitudinal biological samples, including blood, saliva and tissue, for molecular profiling | Molecular profiling to include extraction of DNA for sequencing, RNA for gene expression analysis, expansion of peripheral blood mononuclear cells (PBMCs), and proteins for proteomic studies | Through study completion, expected duration of 5 years | 
| To collect tumour tissue to facilitate molecular analysis of recurrent or metastatic cancers of the head and neck. |  | Through study completion, expected duration of 5 years | 
| To isolate live tumour and immune cells for studies of therapy resistance and biology in cancers of the head and neck. |  | Through study completion, expected duration of 5 years | 
| Retrieval and analysis of archival primary tissue blocks for comparison with metastatic tumour sites. |  | Through study completion, expected duration of 5 years | 
| To correlate assays with clinicopathological data. |  | Through study completion, expected duration of 5 years |