Liquid Biopsy in Head and Neck Cancer

NCT03926468 | Unknown

• 1 other identifier: T17/2019
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Overall survival of patients with head and neck squamous cell carcinoma (HNSCC) remains unsatisfactory due to often advanced clinical stage at diagnosis and high rate of recurrence and second primaries. About 75 % of patients with localized HNSCC are expected to show circulating tumor DNA (ctDNA) pre-treatment. ctDNA reflects tumor genome and disease burden and is termed 'liquid biopsy' (LB) when collected through venous bloodstream. LB has potential to assist in early diagnosis of recurrence and progression, and prediction of response to targeted therapeutic agents. Increased metabolic activity measured 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. The objective is (i) to investigate whether MTV detected with PET-CT correlates to the pattern and amount of genetic alterations in ctDNA of patients with HNSCC referred to radio- (chemo)therapy (RT/CRT). Another objective is (ii) to determine sensitivity of LB compared to PET/CT in detecting residual tumor 3 months after completion of RT/CRT. Third (iii), genetic landscape in LB and fresh tumor samples will be evaluated to detect resistance genes and targets for immunotherapy and surveillance post-treatment. This prospective study includes 30 patients with stage III/IV HNSCC. Before onset and 3 months from RT/CRT, LB is obtained for next-generation DNA sequencing using a commercial platform. ctDNA and digital droplet PCR will be quantified and compared to MTV in simultaneously acquired PET-CT. The investigators hypothesize that LB could assist or replace PET/CT in response monitoring and detection of recurrence after RT/CRT.

Conditions

Head and Neck Squamous Cell Carcinoma

Keywords

Liquid biopsy; FDG PET-CT

Outcome Measures

Primary Outcomes (2)

• Diagnostic performance of circulating tumor DNA (ctDNA) in venous blood sample: Baseline

  Measurement of ctDNA with a novel droplet digital polymerase chain reaction (ddPCR)

  Baseline

• Diagnostic performance of circulating tumor DNA (ctDNA) in venous blood sample: 3-month follow-up

  Measurement of ctDNA with a novel droplet digital polymerase chain reaction

  3-months after completion of therapy (approximately 6 months post-baseline)

Interventions

Liquid biopsy DIAGNOSTIC_TEST

Before onset of treatment, cell-free DNA (cfDNA) is extracted from venous blood sample for next-generation DNA sequencing (NGS) using a commercially available platform (Roche Foundation ACT) For this purpose, 4 x 10 ml of venous blood will be collected from each patient. Two tubes (Streck) will be sent to service provider (Roche), one tube will be used for droplet digital polymerase chain reaction (ddPCR, QX200 Droplet Digital PCR System, BioRad) and ddPRC/NGS analyses and one is collected and stored in Auria Biobank (www.auria.fi) for possible future analyses.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed HNSCC referred to curative multimodality treatment in Hospital District of Southwest Finland

You may qualify if:

• 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

You may not qualify if:

• patients who are not able to sign written informed consent

Sponsors & Collaborators

• Turku University Hospital: lead

Study Sites (1)

Turku University Hospital

Turku, 20521, Finland

Location

Related Publications (3)

• 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.

  PMID: 24553385 BACKGROUND

• 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.

  PMID: 27007578 BACKGROUND

• 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.

  PMID: 27931839 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Circulating tumor DNA (ctDNA) collected from venous blood

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Liquid Biopsy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Biopsy; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Investigative Techniques

Study Officials

• Heikki RI Minn, Prof., MD

  Head, Department of Oncology and Radiotherapy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heikki Minn, Prof., MD

CONTACT

+35823130000; heikki.minn@tyks.fi

Heikki Irjala, MD, PhD

CONTACT

+35823130000; heikki.irjala@tyks.fi

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: April 24, 2019
• Study Start: August 1, 2019
• Primary Completion: June 30, 2022
• Study Completion: December 31, 2022
• Last Updated: June 4, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

FI (1)