Changes in Circulating Tumor-Specific DNA in Patients With Non-Metastatic Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate a blood test to measure circulating tumor DNA (ctDNA). It is hypothesized that ctDNA may identify patients who can be considered for additional therapy. 40 People with non-metastatic non-small cell lung cancer will be asked to take part in this study. Participants will have approximately 3 teaspoons of blood withdrawn from a vein at three different times. These times will be before primary treatment (either surgery or radiation therapy), 1 month after primary treatment, and 4 months after primary treatment.

Detailed Description
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The purpose of this research study is to evaluate a blood test to measure circulating tumor DNA (ctDNA). It is hypothesized that ctDNA may identify patients who can be considered for additional therapy. 40 People with non-metastatic non-small cell lung cancer will be asked to take part in this study. Participants will have approximately 3 teaspoons of blood withdrawn from a vein at three different times. These times will be before primary treatment (either surgery or radiation therapy), 1 month after primary treatment, and 4 months after primary treatment. The total amount of blood withdrawn during the study will be approximately 9 teaspoons. Participants will be followed every 3 months for 12 months to determine if a confirmed recurrence or progression has occurred. Participants will also be asked to complete questionnaires on their quality of life and their smoking behaviors. As part of this study, a blood sample will be obtained and DNA from participants blood sample will be purified. DNA, or deoxyribonucleic acid, stores and transmits inherited traits, such as eye color or blood type. As part of this research project, participant's DNA will be studied in an effort to find out if there are genes that contribute to medical conditions like their cancer that are part of the study. If participants have surgery to have tumor removed or if participants have a biopsy of their tumor, the study would like to take some of the leftover tissue to purify and study the DNA from the tissue sample.

Official Title
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A Pilot Study of Changes in Circulating Tumor-Specific DNA (ctDNA) in Patients With Non-Metastatic Non-Small Cell Lung Cancer

Conditions
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Non Small Cell Lung Cancer

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically confirmed or clinically suspected stage I, II or III NSCLC, provided such patients will be scheduled for a procedure that will provide histologic confirmation of the diagnosis (if the procedure does not provide histologic confirmation of the diagnosis of NSCLC the particular patient will be removed from the study and replaced). Scheduled for treatment with surgery or radiotherapy (Stage I), surgery and chemotherapy (Stage II), or chemoradiotherapy (Stage III). For stage I receiving radiotherapy, treatment must be stereotactic body radiation therapy (SBRT) consisting of 3-5 fractions. Ability to provide blood sample at the following time points: pre-treatment, 1 month post definitive treatment, and 4 post definitive treatment. Ability to understand and the willingness to sign an IRB-approved informed consent document. Staging studies including PET-CT for all patients prior to the initiation of primary treatment, as a pretreatment requirement. For patients with Stage II and III, MRI or CT of the brain is needed prior to the initiation of primary treatment. Patients, however, may be registered and have the pretreatment blood sample collected, provided that the staging studies are being scheduled. Registered patients who are found, after screening tests, to have Stage IV disease will be removed from the study and replaced. Exclusion Criteria: Females who are pregnant History of organ transplant. For stage II and III patients, must be able to receive chemotherapy. Active cardiovascular issues in the past 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients - Stage I treated with surgery<br>ctDNA measures will be taken and descriptive statistics will be estimated. These include means, standard deviations, and 95% confidence intervals. Next, within group changes in ctDNA levels will be measured for each of the four groups. These change values will be estimated with 95% confidence intervals. In addition, paired t-tests will be performed to determine whether there were statistically significant changes in ctDNA levels at time points post-treatment or follow-up. After these paired analyses are performed, an exploratory longitudinal mixed model will be fit to examine the change in ctDNA levels. | |
| Patients - Stage I treated with radiotherapy<br>ctDNA measures will be taken and descriptive statistics will be estimated. These include means, standard deviations and 95% confidence intervals. Next, within group changes in ctDNA levels will be measured for each of the four groups. These change values will be estimated with 95% confidence intervals. In addition, paired t-tests will be performed to determine whether there were statistically significant changes in ctDNA levels at time points post-treatment or follow-up. After these paired analyses are performed, an exploratory longitudinal mixed model will be fit to examine the change in ctDNA levels. | |
| Patients - Stage II treated with surgery & chemotherapy<br>ctDNA measures will be taken and descriptive statistics will be estimated. These include means, standard deviations and 95% confidence intervals. Next, within group changes in ctDNA levels will be measured for each of the four groups. These change values will be estimated with 95% confidence intervals. In addition, paired t-tests will be performed to determine whether there were statistically significant changes in ctDNA levels at time points post-treatment or follow-up. After these paired analyses are performed, an exploratory longitudinal mixed model will be fit to examine the change in ctDNA levels. | |
| Patients - Stage III treated with chemoradiotherapy<br>ctDNA measures will be taken and descriptive statistics will be estimated. These include means, standard deviations and 95% confidence intervals. Next, within group changes in ctDNA levels will be measured for each of the four groups. These change values will be estimated with 95% confidence intervals. In addition, paired t-tests will be performed to determine whether there were statistically significant changes in ctDNA levels at time points post-treatment or follow-up. After these paired analyses are performed, an exploratory longitudinal mixed model will be fit to examine the change in ctDNA levels. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ctDNA levels in patients with Stage I or II (Non-small cell lung cancer) NSCLC | ctDNA levels in patients with Stage I or II NSCLC treated with surgery compared with ctDNA levels in the rest of the cohort. Comparisons will be made at the following time points: Pre-treatment, Post-treatment, and Follow-up. | up to 12 months | 
| Change in ctDNA levels in patients with Stage III NSCLC | ctDNA levels in patients with Stage III NSCLC treated with chemoradiotherapy compared with ctDNA levels in the rest of the cohort. Comparisons will be made at the following time points: Pre-treatment, Post-treatment , and Follow-up. | up to 12 months | 
| Change in ctDNA by treatment group | To determine the change in ctDNA by treatment group at the following time points: change from Pre-treatment to Post-treatment, and change from Pre-treatment to Follow-up. | up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Related Quality of Life- (HRQL) | A two part questionnaire, will be used to assess HRQL: (1) QLQ-C30, a core questionnaire covering general aspects of HRQL, and (2) QLQ-LC13, a lung cancer specific questionnaire. For the QLQ-C30 - All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. For the QLQ-LC13 - All of the scales and single-item measures range in score from 0 to 100. A high score for the scales and single items represents a high level of symptomatology or problems. | up to 12 months | 
| Number of Packs Smoked Per Day | The number of packs of tobacco participants smoked per day will be assessed and recorded | up to 12 months | 
| Number of Years Smoked | The number of years participants smoked will be recorded. | up to 12 months | 
| Number of Participants that have a Smoking Status | Participants will be asked about their current smoking status (yes/no). These answers will be recorded. | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Metastatic Non-Small Cell Lung Cancer, Lung Cancer, circulating tumor-specific DNA (ctDNA), non-invasive diagnostic, Cancer