RecurrenceNCT02420600
The Clinical Relevance of Immune Cells and CTC in HNSCC Patients
An observational study of Recurrence and Metastasis, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
Trial summary
Head and neck squamous cell carcinomas (HNSCCs) are mainly caused by tobacco, alcohol consumption and betel nut chewing and the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate… Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Recurrence, Metastasis, Death
- How many people
- 300 participants
- Where
- 1 siteTaiwan
- Study dates
- Jan 2015to Dec 2018
- How long will I take part?
- 12 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Locally advanced or recurrent/metastatic head and neck cancer
Who may be able to join
- Established head and neck squamous cell carcinoma.
- Age >=20 years old with clear consciousness, decided by free wills.
- Ability to sign informed consent
Who cannot join
- Patient's refusal
- Poor compliance, cannot draw blood for CTCs isolation as time schedule or clinical treatment or follow-up
- Difficult blood sampling
- No more needs for CTCs evaluation, decided by clinicians.
- Inability to comply with study and/or follow-up procedures.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Chang Gung Memorial Hospital
Taoyuan, 333
Tsang-Tang Hsieh, M.D, +886-33281200 ext. 8825, sally6869@cgmh.org.tw
Chia-Hsun Hsieh, M.D,M.S., +886-33281200 ext. 8825, wisdom5000@gmail.com
About this study
Official title: The Clinical Relevance of Immune Cells and Circulating Tumor Cells in Patients With Head and Neck Cancer
Head and neck squamous cell carcinomas (HNSCCs) are mainly caused by tobacco, alcohol consumption and betel nut chewing and the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years.
The worse prognosis of these cancers must certainly be linked to the fact that HNSCCs strongly influence the host immune system. During this process, mesenchymal tumor-like cells are highly mobile and enter quickly adjacent structure (intravasation), from where they travel through lymphatic and blood vessels as circulating tumor cells (CTC), which are single cells with malignant potential detected in the peripheral bloodstream and essential for establishing metastasis.
Read more
Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. Substantial evidence has demonstrated that PD-L1 can deliver an inhibitory signal to PD-1 expressing T cells, leading to suppression of the immune response by inducing apoptosis, energy, unresponsiveness and functional exhaustion of T cells. However, the inhibitory effects of this pathway on the function of cytotoxic T lymphocytes, the main effector cells in HNSCC patients, are not well defined.
In this study aims to solve two main problems: one is to improve and try to optimize current protocols of CTC isolations based on the investigator previous work, which is one of most challenging problems in CTC field to date; the other is to understand the status of immune system in HNSCC patients, especially focusing on PD-1-PD-L1 pathway and its expressions. After series basic experiments of immune cell analysis and conditional adjustment of CTC isolation protocols, the investigator are willing to isolate CTCs and immune cells at a single blood drawing at the same time. A prospective trial will be conducted to elucidate the roles of PD-1 expression lymphocytes and CTC numbers on the clinical outcomes of HNSCC patients.
Read the detailed description
- To establish a platform to increase the efficiency and purity for isolation and enumeration of circulating tumor cells from patients with head and neck cancer.
- Compare the differences and determine the most efficient method or combination of negative, positive selection, optoelectronic dielectrophoresis (ODEP) and flow cytometry sorting technology.
- Negative Selection
- Positive Selection
- ODEP devices
- Flow Cytometry and Sorting System
- Use the upgraded platform and test among different groups for efficiency test. (Planned subjects: healthy donor: n=30; early-stage (stage I=II) patients=9; locally-advanced=9 and metastatic, n=9; total n=60)
- Clinical Enrollment for Device/Method Validation
- To confirm programmed death-1(PD-1) expression could be successfully detected and up-regulated on cytotoxic T cells using cell lines natural killer cell (NK-92).
- Cell Culture of NK-92, OECM-1, SCC-4 and K562
- Immunostaining methods for PD-1 expression
- Flow cytometry for ratio of PD-1 expression
- To observe the functional changes of the cytotoxic T cells with PD-1 expression using cell lines and immunomagnetic bead-based isolation method.
- Positive Isolation for PD-1 Expressing Cells
- CD107a cytotoxicity assay
- Cell-mediated cytotoxicity assays
- Confirm these findings in whole blood sample from healthy donors (n=15) and HNSCC patients (n=15).
- Clinical Enrollment Patients for PD-1 expression in PBMCs, a stage of validation previous findings
- Using the platform established on first-year project, to isolate and check the CTC number from locally advanced or metastatic HNSCC patients for validation.
- To check the ratio of circulating CD56+ cells with PD-1 expression from locally advanced or metastatic HNSCC patients for validation.
- To correlate the clinical relevance of circulating PD-1+CD56 cells and CTCs in locally advanced or metastatic HNSCC patients (N=60 in this year). Another Healthy donors (n=15) will be needed for reference.
- CTC enumeration and sorting technique-Negative Selection Strategy
- Positive Selection
- ODEP devices
- Flow Cytometry and Sorting System
- Clinical Enrollment HNSCC Patients for CTCs and PD-1 ratio
- Conditions
- Recurrence, Metastasis, Death
- Keywords
- Circulating tumor cells, Head and neck cancer, PD-1, natural killer cells, cytotoxic T lymphocytes
- Medical subject headings
- Recurrence, Neoplasm Metastasis, Death, Neoplastic Cells, Circulating, Head and Neck Neoplasms
What is being measured
The primary outcome is the main question the study is designed to answer.
The correlation among CTC numbers, PD-1 expressions and the prognosis of patients.
The CTCs will be isolated and then the number of CTCs will be measured. PD-1 expression from locally advanced or metastatic HNSCC patients will be validated. Measure response or progression events via all available imaging studies, including Chest-Xray, CT scans, or MRI, PET study. The relationship between CTCs number, PD1 expression and time from CTCs checkpoint to disease progression will be analyzed.
Measured: one year
Secondary outcomes (1)
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.
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2017 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for RecurrenceStudies of the same condition, open and under way.
- More trials run by Chang Gung Memorial HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
- Target duration
- 12 Months
Sponsor and investigators
- Lead sponsor
- Chang Gung Memorial Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chia-Hsun Hsieh, M.D, M.S., Principal investigator, Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Lingkou
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02420600
- Sponsor's protocol ID
- CTCHNSCC02
- Other IDs
- CMRPG3E0511-0512
- Status last verified
- Apr 2017
- First submitted
- 15 Apr 2015
- Last updated
- 16 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24844673Chang PH, Wu MH, Liu SY, Wang HM, Huang WK, Liao CT, Yen TC, Ng SH, Chen JS, Lin YC, Lin HC, Hsieh JC. The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing. Cancers (Basel). 2019 Apr 15;11(4):540. doi: 10.3390/cancers11040540.
PubMed 30991692
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Clinical Relevance of Immune Cells and Circulating Tumor Cells in Patients With Head and Neck Cancer
- ClinicalTrials.gov ID
- NCT02420600
- Acronym / sponsor ID
- CTCHNSCC02
- Conditions
- Recurrence, Metastasis, Death
- Keywords
- Circulating tumor cells, Head and neck cancer, PD-1, natural killer cells, cytotoxic T lymphocytes
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Chang Gung Memorial HospitalUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 20 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Head and neck squamous cell carcinomas (HNSCCs) are mainly caused by tobacco, alcohol consumption and betel nut chewing and the sixth most common cancer in the world. Despite significant advances in the treatment modalities involving surgery, radiotherapy, and concomitant chemoradiotherapy, the 5-year survival rate remained below 50% for the past 30 years.
The worse prognosis of these cancers must certainly be linked to the fact that HNSCCs strongly influence the host immune system. During this process, mesenchymal tumor-like cells are highly mobile and enter quickly adjacent structure (intravasation), from where they travel through lymphatic and blood vessels as circulating tumor cells (CTC), which are single cells with malignant potential detected in the peripheral bloodstream and essential for establishing metastasis.
Programmed death 1 (PD-1) and its ligand (PD-L1) play pivotal roles in regulating host immune responses. Substantial evidence has demonstrated that PD-L1 can deliver an inhibitory signal to PD-1 expressing T cells, leading to suppression of the immune response by inducing apoptosis, energy, unresponsiveness and functional exhaustion of T cells. However, the inhibitory effects of this pathway on the function of cytotoxic T lymphocytes, the main effector cells in HNSCC patients, are not well defined.
In this study aims to solve two main problems: one is to improve and try to optimize current protocols of CTC isolations based on the investigator previous work, which is one of most challenging problems in CTC field to date; the other is to understand the status of immune system in HNSCC patients, especially focusing on PD-1-PD-L1 pathway and its expressions. After series basic experiments of immune cell analysis and conditional adjustment of CTC isolation protocols, the investigator are willing to isolate CTCs and immune cells at a single blood drawing at the same time. A prospective trial will be conducted to elucidate the roles of PD-1 expression lymphocytes and CTC numbers on the clinical outcomes of HNSCC patients.
Detailed description
- To establish a platform to increase the efficiency and purity for isolation and enumeration of circulating tumor cells from patients with head and neck cancer.
- Compare the differences and determine the most efficient method or combination of negative, positive selection, optoelectronic dielectrophoresis (ODEP) and flow cytometry sorting technology.
- Negative Selection
- Positive Selection
- ODEP devices
- Flow Cytometry and Sorting System
- Use the upgraded platform and test among different groups for efficiency test. (Planned subjects: healthy donor: n=30; early-stage (stage I=II) patients=9; locally-advanced=9 and metastatic, n=9; total n=60)
- Clinical Enrollment for Device/Method Validation
- To confirm programmed death-1(PD-1) expression could be successfully detected and up-regulated on cytotoxic T cells using cell lines natural killer cell (NK-92).
- Cell Culture of NK-92, OECM-1, SCC-4 and K562
- Immunostaining methods for PD-1 expression
- Flow cytometry for ratio of PD-1 expression
- To observe the functional changes of the cytotoxic T cells with PD-1 expression using cell lines and immunomagnetic bead-based isolation method.
- Positive Isolation for PD-1 Expressing Cells
- CD107a cytotoxicity assay
- Cell-mediated cytotoxicity assays
- Confirm these findings in whole blood sample from healthy donors (n=15) and HNSCC patients (n=15).
- Clinical Enrollment Patients for PD-1 expression in PBMCs, a stage of validation previous findings
- Using the platform established on first-year project, to isolate and check the CTC number from locally advanced or metastatic HNSCC patients for validation.
- To check the ratio of circulating CD56+ cells with PD-1 expression from locally advanced or metastatic HNSCC patients for validation.
- To correlate the clinical relevance of circulating PD-1+CD56 cells and CTCs in locally advanced or metastatic HNSCC patients (N=60 in this year). Another Healthy donors (n=15) will be needed for reference.
- CTC enumeration and sorting technique-Negative Selection Strategy
- Positive Selection
- ODEP devices
- Flow Cytometry and Sorting System
- Clinical Enrollment HNSCC Patients for CTCs and PD-1 ratio
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 12 Months
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Locally advanced or recurrent/metastatic head and neck cancer
Key inclusion criteria (3 listed)
- Established head and neck squamous cell carcinoma.
- Age >=20 years old with clear consciousness, decided by free wills.
- Ability to sign informed consent
Key exclusion criteria (5 listed)
- Patient's refusal
- Poor compliance, cannot draw blood for CTCs isolation as time schedule or clinical treatment or follow-up
- Difficult blood sampling
- No more needs for CTCs evaluation, decided by clinicians.
- Inability to comply with study and/or follow-up procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The correlation among CTC numbers, PD-1 expressions and the prognosis of patients.
Time frame: one year
The CTCs will be isolated and then the number of CTCs will be measured. PD-1 expression from locally advanced or metastatic HNSCC patients will be validated. Measure response or progression events via all available imaging studies, including Chest-Xray, CT scans, or MRI, PET study. The relationship between CTCs number, PD1 expression and time from CTCs checkpoint to disease progression will be analyzed.
1 secondary outcome
Overall survival
Time frame: one year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2017.
- Results publication: PubMed 24844673Hsieh 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.
- Derived from this study: PubMed 30991692Chang PH, Wu MH, Liu SY, Wang HM, Huang WK, Liao CT, Yen TC, Ng SH, Chen JS, Lin YC, Lin HC, Hsieh JC. The Prognostic Roles of Pretreatment Circulating Tumor Cells, Circulating Cancer Stem-Like Cells, and Programmed Cell Death-1 Expression on Peripheral Lymphocytes in Patients with Initially Unresectable, Recurrent or Metastatic Head and Neck Cancer: An Exploratory Study of Three Biomarkers in One-time Blood Drawing. Cancers (Basel). 2019 Apr 15;11(4):540. doi: 10.3390/cancers11040540.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chia-Hsun Hsieh, M.D, M.S. principal investigator
Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Lingkou
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Recurrence and Metastasis, run by Chang Gung Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The correlation among CTC numbers, PD-1 expressions and the prognosis of patients. (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02420600, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2017.