Feasibility of CTCs Isolation for Transcriptomes and Genome Wide Associated Analysis in Post-OP High Risk OSCC Patients. (CTC)

The Feasibility of Circulating Tumor Cells Isolation for Transcriptomes and Genome-wide Associated Analysis in Post-surgically High-risk Oral Cavity Cancer Patients and Its Clinical Significance.

Anti-cancer treatments have been thought to be closely related to their unique genetic alterations. In the past few years, the investigator have used cDNA microarray to delineate the transcriptome profiles of differentially-expressed genes between OSCC tumors and normal epithelium. By supervised hierarachical clustering analysis, the investigator further analyzed and validated the differentially-expressed genes for OSCC tumors. In the investigators' previous research, the investigators have used this strategy to analyze the potential tissue proteins associated with OSCC tumors, indicating the feasibility of this strategy. However, gene detection is a great limitation and challenge in CTCs researches owing to the small number of isolated cells by traditional methods. Fortunately, by means of the investigators' developing high-purity CTCs isolation techniques, some preliminary data implied that isolated CTCs by this method could achieve the criteria of Whole-genome analysis (WGA), which brings the investigators' passion for further investigation.

Study Overview

• Status: Unknown
• Conditions: Oral Cavity Squamous Cell Carcinoma

Detailed Description

First Year

1. Negative Selection Method 2. Positive Selection method (Dynabeads) 3. ODEP devices 4. Flow Cytometry and Sorting System 5. Cell lines for Positive control Second Year &Third year

1. Clinical Trial, Patient Enrollment and Design of Schedule

   The Inclusion criteria and aims are as followings:

   1. Patients with oral cavity squamous cell carcinoma (n=180), with age at diagnosis ≥ 20 years, will be enrolled before surgery at Ear-Nose-Throat department inpatient or outpatient service by Dr. Liao, Dr. Hsieh, Dr. Wang and co-PIs.
   2. All patients will be subgrouped by pathologic features and risk factors Group A (n=90): OSCC, post-surgery, no need for any adjuvant therapy Group B (n=90): OSCC, post-surgery, with major risk factor(s) or 2 minor risk factors Stratification by Risk factors, alcohol, betel nut chewing and cigarette use status
   3. Testing: Circulating tumor cells (CTCs) (x4) and NGS for WGA and transcriptomes (x4)
   4. Endpoints: Loco-regional recurrence, one-year distant metastasis rate, death, second primary tumor occurrence.
   5. Exclusion criteria are: (1) Patient's refusal; (2) Poor compliance, cannot cooperate for blood sampling for CTCs isolation as time schedule or clinical treatment or follow-up (3) Difficult blood sampling; (4) No more needs for CTCs evaluation, decided by clinicians.

2. Whole-Genome Analysis for Cancer Tissue Samples/Circulating Tumor Cells When needed, OncoScan™ FFPE Express Extraction will be performed

   Requirements need to be observed when submitting FFPE slices:

   Slices should be sent in 1.5mL conical vials Tumor samples in sections should have a surface area of 100 square mm (Minimum) to 1000 square mm (Maximum).

   Normal samples in sections should have a surface area of 200 square mm (Minimum) to 1000 square mm (Maximum).

   Section thickness should be 10 micron. The range of sections acceptable per sample is 2-6. Slices for OncoScan analysis and immunohistochemistry study are separated; and will be doubly charged by the Dep. of Clinical Pathology.

   The QIAamp DNA FFPE Tissue Kit is optimized for purification of DNA from FFPE tissue sections.

   OncoScan™ Express Samples will be performed in Chang Gung Memorial Hospital 1J GMRCL CoreLab or Chang Gung University Labs for whole-genome analysis.

3. Negative Selection Method
4. Positive Selection method (Dynabeads)
5. ODEP devices
6. Flow Cytometry and Sorting System

• Study Type: Observational
• Enrollment (Anticipated): 180

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital
    • Contact: Yo-Ting Hsueh; Phone Number: 3703 03-3196200; Email: sally6869@cgmh.org.tw
    • Sub-Investigator: Chia-Hsun Hsieh, M.D, M.S
    • Principal Investigator: Chun-Ta Liao, M.D
    • Sub-Investigator: Chien-Yu Lin, M.D
    • Sub-Investigator: Tzu-Chen Yen, M.D
    • Sub-Investigator: Li-Yu Lee, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with oral cavity squamous cell carcinoma

Description

Inclusion Criteria:

• Patients with oral cavity squamous cell carcinoma (n=180), with age at diagnosis ≥ 20 years, will be enrolled before surgery at Ear-Nose-Throat department inpatient or outpatient service by Dr. Liao, Dr. Hsieh, Dr. Wang and co-PIs.

Exclusion Criteria:

• (1) Patient's refusal; (2) Poor compliance, cannot cooperate for blood sampling for CTCs isolation as time schedule or clinical treatment or follow-up (3) Difficult blood sampling; (4) No more needs for CTCs evaluation, decided by clinicians.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
no need for any adjuvant therapy; Patients with oral cavity squamous cell carcinoma post-surgery no need for any adjuvant therapy
with risk factors; Patients with oral cavity squamous cell carcinoma post-surgery with major risk factor(s) or 2 minor risk factors Stratification by Risk factors, alcohol, betel nut chewing and cigarette use status

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Measure response or progression events via all available imaging studies, including Chest-Xray, CT scans, or MRI, Positron Emission Tomography(PET)study. The relationship between CTCs number and time from CTCs checkpoint to disease progression will be analyzed.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	All causes of death would be documented and the relationship between CTCs number and time from CTCs checkpoint to death will be analyzed.	one year

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Collaborators: Ministry of Science and Technology, Taiwan
• Investigators: Principal Investigator: Chun-Ta Liao, MD, Division of Otolaryngology, Chang Gung Memorial Hospital at Linkou

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Anticipated): July 31, 2019
• Study Completion (Anticipated): July 31, 2020

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 15, 2019
• First Posted (Actual): April 17, 2019

Study Record Updates

• Last Update Posted (Actual): April 17, 2019
• Last Update Submitted That Met QC Criteria: April 15, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Oral Cavity Cancer; distant metastasis; Circulating Tumor Cells; locoregional recurrence; Whole-genome analysis; transcriptomes; second primary tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: CTCNGS002; MOST104-2314-B-182A-073-MY3 (Other Identifier: Grantor or Funder MOST104-2314-B-182A-073-MY3)

Drug and device information, study documents

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