- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03926468
Liquid Biopsy in Head and Neck Cancer
Genetic Profiling by Liquid Biopsy for Initial Characterization and Response Monitoring of Head and Neck Squamous Cell Carcinoma (HNSCC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Background
Head and neck squamous cell carcinoma (HNSCC) stands as the sixth most common cancer worldwide. The overall 5-year survival is approximately 50 % due to often advanced clinical stage at diagnosis, high rate of treatment resistance, and high incidence of second cancers. Currently there are no useful biomarkers for surveillance or diagnosis of recurrent HNSCC.
Liquid biopsy (LB)
Circulating tumor DNA (ctDNA) is tumor-derived fragmented DNA circulating freely in the bloodstream. Apoptosis and necrosis due to rapid cell growth and increased cell turnover contribute to release of ctDNA in circulation of patients with cancer even without disseminated disease. ctDNA reflects tumor genome and may also reflect disease burden. Due to these properties and easy accessibility collection of ctDNA through venous blood has been termed as 'liquid biopsy'. Approximately 75-90 % of patients with localized or untreated HNSCC are expected to show ctDNA pre-treatment.
Applications of liquid biopsy in HNSCC
Potential clinical applications of liquid biopsy (LB) are manifold and include diagnosis of recurrence or progression, and disease surveillance. While ctDNA contains the same mutations present in original tumor, LB can be used to guide targeted therapies if local treatment is not feasible. In HNSCC, these features render study of LB attractive since early diagnosis of treatment failure increases possibilities for curative approach. ctDNA reflects tumor heterogeneity and findings in surveillance samples are more likely to characterize resistant subpopulations compared to pre-treatment changes. Recently, immune checkpoint inhibition with monoclonal antibodies against programmed cell death (PD-1) have demonstrated activity against recurrent or metastatic HNSCC. LB together with evaluation of expression of PD-1 ligand (PD-L1) can assess mutational load thus assisting in screening patients who may benefit from immunotherapy.
Metabolic imaging - current standard for detection of recurrent HNSCC
Increased metabolic activity detected in positron emission tomography-computed tomography (PET-CT) is currently the most sensitive technique to detect residual cancer or progression of HNSCC after curative treatment. High metabolically active tumor volume (MTV) is associated with treatment resistance and shows independent prognostic significance. While PET-CT shows excellent sensitivity, it may lead to false positive findings caused by inflammation or other conditions having increased cellular metabolic rate. Furthermore, metabolic imaging does not elucidate resistance mechanisms nor does it assist in planning of targeted treatments. Whether LB could assist or replace PET/CT in response monitoring and detection of recurrence remains thus far unknown.
Study objectives
i) To investigate whether MTV detected in PET-CT correlates to pattern and amount of genetic alterations in ctDNA of patients with HNSCC referred to radiotherapy (RT) or chemoradiotherapy (CRT) ii) To determine whether LB is more sensitive than PET/CT in detecting residual tumor three months after completion of RT or CRT iii) To evaluate exhaustive genetic landscape of patients with locally advanced HNSCC in order to characterize resistance or target genes for alternative treatments including (but not limited to) immunotherapy, antibodies against epidermal growth factor receptor (EGFR), and hypoxia- and virus-activated compounds iv) To validate a novel digital droplet polymerase chain reaction (PCR) technique for non-invasive surveillance of patients at high risk for recurrence of HNSCC
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Heikki Minn, Prof., MD
- Phone Number: 30149 +35823130000
- Email: heikki.minn@tyks.fi
Study Contact Backup
- Name: Heikki Irjala, MD, PhD
- Phone Number: 30411 +35823130000
- Email: heikki.irjala@tyks.fi
Study Locations
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Turku, Finland, 20521
- Turku University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- histologically confirmed head and neck squamous cell carcinoma (HNSCC)
- WHO performance status 0-2
- clinical stage III patients with bulky T3 primary +/- neck metastasis
- all stage IV patients
- referral to definitive radiotherapy or chemoradiotherapy or multimodality treatment
Exclusion Criteria:
- patients who are not able to sign written informed consent
Study Plan
How is the study designed?
Design Details
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Diagnostic performance of circulating tumor DNA (ctDNA) in venous blood sample: Baseline
Time Frame: Baseline
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Measurement of ctDNA with a novel droplet digital polymerase chain reaction (ddPCR)
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Baseline
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Diagnostic performance of circulating tumor DNA (ctDNA) in venous blood sample: 3-month follow-up
Time Frame: 3-months after completion of therapy (approximately 6 months post-baseline)
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Measurement of ctDNA with a novel droplet digital polymerase chain reaction
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3-months after completion of therapy (approximately 6 months post-baseline)
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Heikki RI Minn, Prof., MD, Head, Department of Oncology and Radiotherapy
Publications and helpful links
General Publications
- Bettegowda C, Sausen M, Leary RJ, Kinde I, Wang Y, Agrawal N, Bartlett BR, Wang H, Luber B, Alani RM, Antonarakis ES, Azad NS, Bardelli A, Brem H, Cameron JL, Lee CC, Fecher LA, Gallia GL, Gibbs P, Le D, Giuntoli RL, Goggins M, Hogarty MD, Holdhoff M, Hong SM, Jiao Y, Juhl HH, Kim JJ, Siravegna G, Laheru DA, Lauricella C, Lim M, Lipson EJ, Marie SK, Netto GJ, Oliner KS, Olivi A, Olsson L, Riggins GJ, Sartore-Bianchi A, Schmidt K, Shih lM, Oba-Shinjo SM, Siena S, Theodorescu D, Tie J, Harkins TT, Veronese S, Wang TL, Weingart JD, Wolfgang CL, Wood LD, Xing D, Hruban RH, Wu J, Allen PJ, Schmidt CM, Choti MA, Velculescu VE, Kinzler KW, Vogelstein B, Papadopoulos N, Diaz LA Jr. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014 Feb 19;6(224):224ra24. doi: 10.1126/scitranslmed.3007094.
- Mehanna H, Wong WL, McConkey CC, Rahman JK, Robinson M, Hartley AG, Nutting C, Powell N, Al-Booz H, Robinson M, Junor E, Rizwanullah M, von Zeidler SV, Wieshmann H, Hulme C, Smith AF, Hall P, Dunn J; PET-NECK Trial Management Group. PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer. N Engl J Med. 2016 Apr 14;374(15):1444-54. doi: 10.1056/NEJMoa1514493. Epub 2016 Mar 23.
- Castelli J, De Bari B, Depeursinge A, Simon A, Devillers A, Roman Jimenez G, Prior J, Ozsahin M, de Crevoisier R, Bourhis J. Overview of the predictive value of quantitative 18 FDG PET in head and neck cancer treated with chemoradiotherapy. Crit Rev Oncol Hematol. 2016 Dec;108:40-51. doi: 10.1016/j.critrevonc.2016.10.009. Epub 2016 Oct 29.
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- T17/2019
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Head and Neck Squamous Cell Carcinoma
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Wake Forest University Health SciencesNational Cancer Institute (NCI)RecruitingRecurrent Head and Neck Squamous Cell Carcinoma | Advanced Head and Neck Squamous Cell Carcinoma | Metastatic Head-and-neck Squamous-cell Carcinoma | Locally Advanced Head and Neck Squamous Cell Carcinoma | Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck | Stage IV Cutaneous...United States
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