Clinical trial NCT02791607: The Clinical Relevance of P16 Expressing CTCs Detection Comparing With HPV Infection in Cancer Tissue in HNSCC Patients.
Official title: Technical Development of P16-INk4A-expressing Circulating Tumor Cells Detection Comparing With Human Papillomavirus Infection in Cancer Tissue in Patients With Head and Neck Cancer and Its Clinical Relevance.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Recurrence
Metastasis
Death
Keywords: Circulating tumor cells
Head and neck cancer
Survival Prognosis
P16Ink4A
HPV
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2016-06-07
Enrollment: 150
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will be conducted in three branch hospitals of Chang Gung Memorial Hospital, Taiwan including Keelung, Linkou, Taipei. Locally advanced or recurrent/metastatic head and neck cancer

Brief summary: HNSCC is the 4th highest incidence of cancer and 6th of cancer death of the males in Taiwan. Because the patients were mainly middle-aged male, the disease eventually resulted in a huge loss of labor force, productivity and a huge burden of family supports and medicinal costs. Currently, the primary treatments of HNSCC are mainly surgery, radiotherapy, chemotherapy or targeted therapy or concurrent chemoradiotherapy. Compared to oral cavity cancer, patients with pharyngeal cancer would possibly harbor HPV infections and have better treatment outcomes, prognosis and survival with clinically significance; however, the investigator's reports showed quite the opposite prognostic value in oral cavity cancer. The inconsistent data urges us to investigate further. Fortunately, in recent years, The investigator have developed a new method for isolation and detection of CTCs in HNSCC patients.The investigator's data found that high level of CTCs in patients with HNSCC and might be associated with disease prognosis, response to treatment and distant metastasis. This novel tool enhances the studies addressing on metastases or recurrence process in HNSCC patients. However, the investigator did not focus whether if the dynamic change of CTCs and specific surface markers on CTCs, such as P16+ CTCs are clinically meaningful.

Therefore, in the first year, the investigator will utilize the investigator's developing device and protocol to isolate high-purity CTCs to further identify P16+ on CTCs. In the following 2 years of the project, the investigator will enroll 150 freshly diagnosed patients with oral cavity, oropharyngeal, hypopharyngeal and laryngeal cancer at all stages (75 P16+ and 75 P16- patients) and 30 healthy donors for cell line tests, and then analyze CTCs, background white blood cells signals, and their initial biopsied tissue for P16 positivity test. Further statistical tests with clinical conditions (disease status, treatment effects, progression or distant metastasis and death) will be performed to elucidate their clinical significance.Hopefully, the investigator will clarify the clinical significance of circulating P16 expression status on CTCs by this study and provide a new biomarker for clinical cancer care.

Detailed description: 1. Establish a protocol and a practical platform to longitudinally isolate, enumerate CTCs in patients with HPV+-head and neck cancer during the treatment course.
2. Elucidate the clinical significance of P16 INK4A -expressing CTCs to cancer status and treatment response.
3. Verify that dynamically monitoring P16 status and changes during anti-cancer treatment is feasible and clinically meaningful to survival or treatment responses.
4. Analyze different habitual conditions, i.e. alcohol, cigarette and betel nut use to P16-expressing CTCs.
5. Establish a good model to follow-up a specific surface marker on CTCs, which could be possibly utilized in other cancers with their particular markers (i.e. CEA on gastric cancer, Her2 on breast cancer)

Eligibility criteria: Inclusion Criteria:

* histologically or cytopathologically proven head and neck squamous cell carcinoma Age ≥ 20 years. Measurable or evaluable disease according to Response Evaluation Criteria In Solid Tumors(RECIST) criteria.

Ability to sign informed consent.

Exclusion Criteria:

* Prior cancers within 5 years, except for non-melanoma skin cancers, and in situ cervical cancers.

Inability to completely with study and/or follow-up procedures.

Primary outcomes:
measure: Progression-free survival
timeFrame: one year
Secondary outcomes:
measure: Overall survival
timeFrame: one year
Other outcomes:
Locations:
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou
name: Chia-Hsun Hsieh, M.D, M.S
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hsieh JC, Lin HC, Huang CY, Hsu HL, Wu TM, Lee CL, Chen MC, Wang HM, Tseng CP. Prognostic value of circulating tumor cells with podoplanin expression in patients with locally advanced or metastatic head and neck squamous cell carcinoma. Head Neck. 2015 Oct;37(10):1448-55. doi: 10.1002/hed.23779. Epub 2014 Jul 24.
citation: Huang SB, Wu MH, Lin YH, Hsieh CH, Yang CL, Lin HC, Tseng CP, Lee GB. High-purity and label-free isolation of circulating tumor cells (CTCs) in a microfluidic platform by using optically-induced-dielectrophoretic (ODEP) force. Lab Chip. 2013 Apr 7;13(7):1371-83. doi: 10.1039/c3lc41256c.
citation: Huang SB, Wang SS, Hsieh CH, Lin YC, Lai CS, Wu MH. An integrated microfluidic cell culture system for high-throughput perfusion three-dimensional cell culture-based assays: effect of cell culture model on the results of chemosensitivity assays. Lab Chip. 2013 Mar 21;13(6):1133-43. doi: 10.1039/c2lc41264k.