ctDNA as a Biomarker for Treatment Response in HNSCC (PECAN)

Prospective Study Evaluating ctDNA as a Biomarker for Treatment Response in Head and Neck Squamous Cell Carcinoma'

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.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Squamous Cell of Head and Neck
• Intervention / Treatment: Other: Blood draw

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Antoni van Leeuwenhoek

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: blood draw; Blood 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.	Other: Blood draw; Blood will be drawn to assess ctDNA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	ctDNA biomarker	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	ctDNA biomarker	2 years
Levels of ctDNA at the time of corresponding conventional imaging in relation to disease occurrence.	ctDNA biomarker	3 years
The number of traceable mutations found in blood / saliva in comparison with mutations found in tissue biopsies.	ctDNA biomarker	3 years
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.	ctDNA biomarker	3 years
Levels of ctDNA in blood compared to saliva at the same time points.	ctDNA biomarker	At study completion, after 3 years
Levels of ctDNA before treatment compared to other clinical/biological parameters in the prediction of treatment response.	ctDNA biomarker	3 years

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Investigators: Principal Investigator: Abrahim Al-Mamgani, MD, PhD, Antoni van Leeuwenhoek

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): August 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ctDNA
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: N18PCN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patients sign for participation in this study and not for use in other studies

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No