Carcinoma, Non-Small-Cell LungNCT05737589
Circulating Tumor DNA and T Cell Repertoire Predict Radiotherapeutic Outcomes in NSCLC Patients With Brain Metastasis
An observational study of Carcinoma, Non-Small-Cell Lung and Brain Metastases, run by Xiaorong Dong at 1 site in China.
Trial summary
Collection of ctDNA and TCR data to predict the efficacy and prognosis of brain radiotherapy in patients with brain metastases from non-small cell lung cancer (NSCLC) in a comprehensive manner Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Brain Metastases
- What is being tested?
- Whole-brain radiotherapy
- Type of treatment
- Surgery or procedure
- How many people
- 50 participants
- Where
- 1 siteChina
- Study dates
- 13 Feb 2023to 1 Oct 2024
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: A group of non-small cell lung cancer patients with brain metastasis who have never received radiotherapy
Who may be able to join
- Age > 18 years
- Patients must have histologically or cytologically confirmed NSCLC and imaging-confirmed primary non-small cell lung cancer with brain metastases
- ECOG PS score of 0-2
- At least 1 lesion meeting RECIST 1.1 target lesion (TL) criteria at baseline. Must have baseline assessment imaging of the tumor by CT or MRI scan within 28 days prior to treatment
- No prior radiation therapy to the tumor, including but not limited to whole brain radiotherapy, prophylactic brain irradiation, stereotactic radiation therapy, etc.
- Major organ function indicators meet the criteria for conventional radiation therapy Adequate organ and bone marrow function is defined as follows
Show all 15Show fewer
- Hemoglobin ≥ 9.0 g/dL
- absolute neutrophil count ≥ 1.5 × 109 / L
- Platelet count ≥ 100 × 109 / L
- Serum bilirubin ≤ 1.5 × the upper limit of normal (ULN). The above criteria were not applied to patients diagnosed with Gilbert's syndrome, but these patients were allowed to be enrolled after consultation between the study physician and their primary care physician.
- Alanine aminotransferase ALT or aspartate aminotransferase AST ≤ 2.5 × ULN
- Creatinine clearance (CL) > 40 mL/min calculated or actually measured according to the Cockcroft-Gault method (based on actual body weight) Men. Creatinine CL = Body weight (kg) × (140 - age) (mL/min) 72 x serum creatinine (mg/dL) Females. Creatinine CL = Body weight (kg) × (140 - age) × 0.85 (mL/min) 72 × serum creatinine (mg/dL)
- Female subjects of childbearing age must exclude pregnancy
- Life expectancy >12 weeks
- Body weight >30Kg
Who cannot join
- History of allogeneic organ transplantation
- Active or previously documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (except diverticular disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener's syndrome [granulomatous vasculitis, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis, etc.])
- History of active primary immunodeficiency
- Other malignancies within the last 3 years.
- Presence of uncontrolled co-morbidities including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmias, active interstitial lung disease, a severe chronic gastrointestinal disease with diarrhea or mental illness that limits compliance with study requirements, significantly increases the risk of AE or affects the patient's life/ social conditions
- Active infection at the time of treatment, including tuberculosis (clinical assessment includes history, physical examination, imaging findings, and tuberculosis screening consistent with local clinical practice), hepatitis B (known hepatitis B surface antigen positive [HBsAg] result), hepatitis C virus (HCV) or human immunodeficiency virus (HIV 1/2 antibody positive). Patients with previous hepatitis B virus (HBV) infection or cured HBV infection (defined as the presence of positive hepatitis B core antibodies and negative HBsAg) may participate in this study. patients with positive HCV antibodies who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction only may participate in this study.
- Stage IV NSCLC according to the 8th edition of the International Society for the Study of Lung Cancer Thoracic Oncology Staging Manual
- Histological findings of NSCLC with mixed small cell component
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Integrated Circulating Tumor DNA and T Cell Repertoire Predict Radiotherapeutic Response and Outcome in Non-small Cell Lung Cancer Patients With Brain Metastasis
Collection of ctDNA and TCR data to predict the efficacy and prognosis of brain radiotherapy in patients with brain metastases from non-small cell lung cancer (NSCLC) in a comprehensive manner
Read the detailed description
The scarcity of biopsies or focal resections for brain metastases limits the discovery of biomarkers for diagnosing and prognosis of NSCLC patients with brain metastases. Circulating tumor DNA (ctDNA) is derived from the necrosis, apoptosis, and secretion of tumor cells and is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF). Genomic alterations in blood and CSF ctDNA are prognostic markers in NSCLC patients with brain metastases. Still, they have limited predictive power. T cell-mediated immune responses are essential to suppress carcinogenesis and metastasis in NSCLC. Targeted sequencing in the highly variable complementarity determining region 3 (CDR3) region of the T cell receptor (TCR) β-chain provides a powerful approach to quantifying the diversity of T cells. Radiotherapy causes antigen exposure through direct local destruction of cancer cells, which activates the local and systemic immune system. Radiotherapy can also cause intracellular DNA damage, and the ensuing mutations in DNA mismatch repair defects may increase neoantigen load, triggering an immune response. The TCR, closely related to immune system modifications, can also be altered by radiotherapy. However, no clinical studies have explored ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases. Therefore, we retrieved the visit data of 50 patients with advanced NSCLC brain metastases who received brain radiotherapy through the hospital electronic medical record system and recorded the ctDNA and TCR values of patients' blood and CSF at baseline (within 2 weeks before radiotherapy), T0 (within 24 hours after the completion of radiotherapy) and T28 (28 days after the completion of radiotherapy), disease progression recurrence and survival time by examining. The dynamic changes of ctDNA and TCR during brain radiotherapy were studied to comprehensively assess the ability of ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Brain Metastases
- Being tested
- Whole-brain radiotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Whole-brain radiotherapyRadiation
Also called Stereotactic radiotherapy
Radiotherapy is administered to the patient's brain lesions, and the subject's specific treatment plan is developed by two specialized physicians.
| Study group | Role | What they receive |
|---|---|---|
| Observation group | This is an observational study, no interventions will be applied to patients in the observation group, and only blood and cerebrospinal fluid ctDNA and TCR data of patients with brain metastases from non-small cell lung cancer treated with radiotherapy will be recorded to predict patient prognosis. Peripheral blood and CSF samples were collected at baseline, 24 h (T0), and 28 days (T28) after completion of radiotherapy and underwent deep sequencing of ctDNA and TCR. The 6-month response rates of brain metastases and systemic lesions were evaluated based on Response Evaluation Criteria in Solid Tumors version 1.1 for further study. Receives: Radiation: Whole-brain radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
overall survival (OS)
OS is defined as the time elapsed between the initiation of radiotherapy and mortality from any cause.
Measured: February 13, 2023-February 13, 2024
Secondary outcomes (2)
progression-free survival (PFS)
PFS is defined as the time elapsed between the start of radiotherapy and the first sign of disease progression or death from any cause.
Measured: February 13, 2023-February 13, 2024
intracranial PFS (iPFS)
The duration from the start of radiotherapy to the first intracranial lesion progression or death from any cause is referred to as iPFS.
Measured: February 13, 2023-February 13, 2024
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2023
- Study start13 Feb 2023 (estimated)
- Primary completion13 Feb 2024 (estimated)
- Study completion1 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- 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
- Retrospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiaorong Dong
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xiaorong Dong, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
- Investigators
- Xiaorong Dong, Dr., Study chair, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05737589
- Sponsor's protocol ID
- DTO-20230201
- Status last verified
- Feb 2023
- First submitted
- 12 Feb 2023
- Last updated
- 21 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no data-sharing plan for other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrated Circulating Tumor DNA and T Cell Repertoire Predict Radiotherapeutic Response and Outcome in Non-small Cell Lung Cancer Patients With Brain Metastasis
- ClinicalTrials.gov ID
- NCT05737589
- Acronym / sponsor ID
- DTO-20230201
- Conditions
- Carcinoma, Non-Small-Cell Lung, Brain Metastases
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Xiaorong DongUniversity, hospital or other
- Study start
- 13 Feb 2023 (estimated)
- Primary completion
- 13 Feb 2024 (estimated)
- Study completion
- 1 Oct 2024 (estimated)
- First posted
- 21 Feb 2023 (actual)
- 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.
Collection of ctDNA and TCR data to predict the efficacy and prognosis of brain radiotherapy in patients with brain metastases from non-small cell lung cancer (NSCLC) in a comprehensive manner
Detailed description
The scarcity of biopsies or focal resections for brain metastases limits the discovery of biomarkers for diagnosing and prognosis of NSCLC patients with brain metastases. Circulating tumor DNA (ctDNA) is derived from the necrosis, apoptosis, and secretion of tumor cells and is widely distributed in various body fluids, including peripheral blood and cerebrospinal fluid (CSF). Genomic alterations in blood and CSF ctDNA are prognostic markers in NSCLC patients with brain metastases. Still, they have limited predictive power. T cell-mediated immune responses are essential to suppress carcinogenesis and metastasis in NSCLC. Targeted sequencing in the highly variable complementarity determining region 3 (CDR3) region of the T cell receptor (TCR) β-chain provides a powerful approach to quantifying the diversity of T cells. Radiotherapy causes antigen exposure through direct local destruction of cancer cells, which activates the local and systemic immune system. Radiotherapy can also cause intracellular DNA damage, and the ensuing mutations in DNA mismatch repair defects may increase neoantigen load, triggering an immune response. The TCR, closely related to immune system modifications, can also be altered by radiotherapy. However, no clinical studies have explored ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases. Therefore, we retrieved the visit data of 50 patients with advanced NSCLC brain metastases who received brain radiotherapy through the hospital electronic medical record system and recorded the ctDNA and TCR values of patients' blood and CSF at baseline (within 2 weeks before radiotherapy), T0 (within 24 hours after the completion of radiotherapy) and T28 (28 days after the completion of radiotherapy), disease progression recurrence and survival time by examining. The dynamic changes of ctDNA and TCR during brain radiotherapy were studied to comprehensively assess the ability of ctDNA and TCR to predict the efficacy and prognosis of brain radiotherapy in patients with NSCLC brain metastases.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observation group | – | Radiation: Whole-brain radiotherapyThis is an observational study, no interventions will be applied to patients in the observation group, and only blood and cerebrospinal fluid ctDNA and TCR data of patients with brain metastases from non-small cell lung cancer treated with radiotherapy will be recorded to predict patient prognosis. Peripheral blood and CSF samples were collected at baseline, 24 h (T0), and 28 days (T28) after completion of radiotherapy and underwent deep sequencing of ctDNA and TCR. The 6-month response rates of brain metastases and systemic lesions were evaluated based on Response Evaluation Criteria in Solid Tumors version 1.1 for further study. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A group of non-small cell lung cancer patients with brain metastasis who have never received radiotherapy
Key inclusion criteria (15 listed)
- Age > 18 years
- Patients must have histologically or cytologically confirmed NSCLC and imaging-confirmed primary non-small cell lung cancer with brain metastases
- ECOG PS score of 0-2
- At least 1 lesion meeting RECIST 1.1 target lesion (TL) criteria at baseline. Must have baseline assessment imaging of the tumor by CT or MRI scan within 28 days prior to treatment
- No prior radiation therapy to the tumor, including but not limited to whole brain radiotherapy, prophylactic brain irradiation, stereotactic radiation therapy, etc.
Key exclusion criteria (8 listed)
- History of allogeneic organ transplantation
- Active or previously documented autoimmune or inflammatory disease (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis (except diverticular disease), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener's syndrome [granulomatous vasculitis, Graves' disease, rheumatoid arthritis, pituitary inflammation, uveitis, etc.])
- History of active primary immunodeficiency
- Other malignancies within the last 3 years.
- Presence of uncontrolled co-morbidities including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmias, active interstitial lung disease, a severe chronic gastrointestinal disease with diarrhea or mental illness that limits compliance with study requirements, significantly increases the risk of AE or affects the patient's life/ social conditions
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Whole-brain radiotherapyAlso: Stereotactic radiotherapyRadiotherapy is administered to the patient's brain lesions, and the subject's specific treatment plan is developed by two specialized physicians. | Radiation | Observation group |
Primary outcome
overall survival (OS)
Time frame: February 13, 2023-February 13, 2024
OS is defined as the time elapsed between the initiation of radiotherapy and mortality from any cause.
2 secondary outcomes
progression-free survival (PFS)
Time frame: February 13, 2023-February 13, 2024
intracranial PFS (iPFS)
Time frame: February 13, 2023-February 13, 2024
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
- Individual participant dataSharing planned: No. There is no data-sharing plan for other researchers.
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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.
Xiaorong Dong, Dr. study chair
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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 Carcinoma, Non-Small-Cell Lung and Brain Metastases, run by Xiaorong Dong at 1 site in China.
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 15 inclusion and 8 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 21 Feb 2023. 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 China. 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?
Contact Xiaorong Dong, Dr. (13986252286, xiaorongdong@hust.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
overall survival (OS) (time frame: February 13, 2023-February 13, 2024). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Feb 2023.