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ctDNA as a Biomarker for Treatment Response in HNSCC

Not Applicable
Completed
Conditions
Carcinoma, Squamous Cell of Head and Neck
Interventions
Other: Blood draw
Registration Number
NCT03540563
Lead Sponsor
The Netherlands Cancer Institute
Brief Summary

Tumours continually shed DNA into the circulation, where it can be accessed. This circulating tumour DNA (ctDNA) directly reflects tumour burden and has great potential to be a sensitive biomarker for treatment recurrence. These "liquid biopsies" could give a more real-time picture of the genomic status and evolution of a tumour and can be easily assessed for measurement of different biomarkers. However, in head and neck squamous cell carcinoma (HNSCC) patients treated with primary curative radiotherapy, data regarding ctDNA kinetics and its correlation with outcome are scarce. A new or additional tool for response evaluation next to or instead of conventional imaging after treatment would be beneficial to detect recurrences in an earlier stage, thereby increasing the chances of success of salvage therapy. More importantly, an early response parameter during treatment could help to identify patients that have a good treatment response and might benefit from treatment adaptation. With this study, we aim to reveal ctDNA as an effective tool for future dose (de)-escalation trials in HNSCC.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
70
Inclusion Criteria
  • ≥ 18 years of age
  • Stage II-IV carcinoma of the larynx, hypopharynx, oral cavity or HPV negative oropharynx or stage II-III HPV positive oropharyngeal carcinoma, histologically confirmed according to the American Joint Committee on Cancer (AJCC) staging manual 8th edition
  • Indication for primary curative radiotherapy with or without concurrent radio sensitizer
  • WHO performance status 0-2
  • Signed written IC
Exclusion Criteria
  • Metastatic disease
  • Radiotherapy with palliative intent
  • Diagnosis of any other malignancy within 5 years prior to start of treatment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or of the cervix, or low-grade (Gleason 6 or below) prostate cancer on surveillance with no plans for treatment intervention (e.g. surgery, radiation or castration).

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
blood drawBlood drawBlood and saliva specimens will be taken for ctDNA analysis at baseline, weekly during treatment and at 2 weeks after treatment. During follow up both blood and saliva will be obtained in combination with a CT/MRI scan on the same day at 3 months, 6 months, 1 year and 2 years after treatment.
Primary Outcome Measures
NameTimeMethod
The number of patients in which ctDNA measurement (in amplifiable copies per millilitre blood and saliva) accurately predicts treatment outcome within 2 years after treatment, in terms of FFP.2 years

ctDNA biomarker

Secondary Outcome Measures
NameTimeMethod
Levels of ctDNA at the time of corresponding conventional imaging in relation to disease occurrence.3 years

ctDNA biomarker

The number of traceable mutations found in blood / saliva in comparison with mutations found in tissue biopsies.3 years

ctDNA biomarker

Levels of ctDNA in blood compared to saliva at the same time points.At study completion, after 3 years

ctDNA biomarker

The tumours' genomic status and epigenetic evolution over time under pressure of radiotherapy, in terms of number of different detectable mutations at all specified time points.3 years

ctDNA biomarker

CtDNA kinetics (clearance time, drop below a certain level, complete absence, etc.) during radiotherapy as a predictor for disease recurrence within 2 years after treatment, in terms of FFP.2 years

ctDNA biomarker

Levels of ctDNA before treatment compared to other clinical/biological parameters in the prediction of treatment response.3 years

ctDNA biomarker

Trial Locations

Locations (1)

Antoni van Leeuwenhoek

🇳🇱

Amsterdam, Netherlands

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