ARGONAUT: Stool and Blood Sample Bank for Cancer Patients

Study Overview
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Brief Summary
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ARGONAUT is a longitudinal, prospective, observational study that will enroll up to 5,000 advanced-stage cancer patients of diverse racial backgrounds to collect data used to develop precision microbiome medicines and for the identification of clinically actionable cancer-specific biomarkers to guide therapeutic decisions. Four types of solid tumor cancers will be profiled including non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), colorectal cancer (CRC) and pancreatic cancer. Healthy control subjects without a cancer diagnosis will also be studied, comprised of individuals at high risk for CRC and healthy individuals at low risk for CRC. Risk assessment will be based on family history or past neoplastic findings during CRC screening. Data collected from this study will be used to develop the most effective new therapies, via microbiome optimization, all to the benefit of patients and the physicians treating them. Stool and blood samples will be collected longitudinally and analyzed to determine the impact of gut microbiome composition and function on the immune system and efficacy of the treatment. Currently enrolling the CRC, high risk, and low risk cohorts. Subjects who meet the entry criteria will provide up to 5 samples each of blood and stool over a 2-year period. Approximately 10%-20% of the subjects will provide colon tissue samples, either from research biopsies during Standard of Care (SOC) screening colonoscopy or retained surgical tissue from colectomy. Electronic health records will be obtained at various times for up to 8 years, to collect tumor imaging results and any other updated medical data, with no additional samples collected. In select cases, stool and blood samples will be collected beyond 2 years.

Official Title
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ARGONAUT: Development and Analysis of a Blood and Stool Sample Bank for Cancer Patients, Enabling the Systematic Study of the Effect of Gut Microbiomes on Response to Treatment

Conditions
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Non-small Cell Lung Cancer, Colorectal Cancer, Triple Negative Breast Cancer, Pancreas Cancer

Intervention / Treatment
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* Drug: Immunotherapy
* Drug: Chemotherapy
* Procedure: CRC surgical resection
* Procedure: Colonoscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women who are ≥ 18 years old with stage III or stage IV non-small cell lung cancer (NSCLC), colorectal cancer, triple-negative breast cancer, or pancreatic cancer treated by a particular cancer treatment for the first time, OR healthy subjects undergoing a standard of care colonoscopy Subjects able to provide written informed consent Exclusion Criteria: Subjects with known HIV, Hepatitis A, Hepatitis B, Hepatitis C, or SARS-CoV2 Subjects without the mental capacity to complete either a written or online questionnaire, alone or with assistance, or make sound decisions Women who are pregnant or who plan on becoming pregnant Women who are nursing

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NSCLC<br>Stage 3 or stage 4 non-small cell lung cancer patients, being administered checkpoint inhibitor therapy for the first time. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted. | Drug: Immunotherapy<br>* Checkpoint inhibitor<br>|
| Triple-negative breast cancer<br>Stage 3 or stage 4 metastatic triple-negative breast cancer patients, being administered any type of treatment that the patient has not experienced before. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted. | Drug: Chemotherapy<br>* Any form of chemotherapy<br>|
| Colorectal cancer<br>Stage 3 or stage 4 colorectal cancer patients, being administered any type of treatment that the patient has not experienced before. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted. | Drug: Immunotherapy<br>* Checkpoint inhibitor<br>Drug: Chemotherapy<br>* Any form of chemotherapy<br>Procedure: CRC surgical resection<br>* Surgical resection to remove colorectal cancer<br>|
| Pancreatic cancer<br>Stage 3 or stage 4 pancreatic cancer patients, being administered any type of treatment that the patient has not experienced before. Dosage form, dosage, frequency and duration will be either standard of care and accessed via normal commissioning arrangements, or will be part of an ethics-approved clinical trial, where co-enrollment into an observational study is permitted. | Drug: Immunotherapy<br>* Checkpoint inhibitor<br>Drug: Chemotherapy<br>* Any form of chemotherapy<br>|
| High risk for colorectal cancer<br>Subjects undergoing a standard-of-care colonoscopy for colorectal cancer (CRC) screening considered at high risk for CRC due to either 1) one or more first degree relatives with a history of CRC, or 2) a personal history of colorectal cancer, advanced adenoma as defined by USMSTF guidelines on colorectal cancer, or 3 or more non-advanced adenomas in a single screening or surveillance encounter (synchronous). | Procedure: Colonoscopy<br>* Standard-of-care colonoscopy for CRC screening<br>|
| Low risk for colorectal cancer<br>Subjects undergoing a standard-of-care colonoscopy for colorectal cancer (CRC) screening, who are not considered high risk for CRC based on family history or prior colonoscopy findings. | Procedure: Colonoscopy<br>* Standard-of-care colonoscopy for CRC screening<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether the microbiome composition can predict progression-free survival | Whole genome sequencing and metabolomics will be used to characterize the patient's microbiome, and whether there is any correlation with response to treatment | 6-12 months | 
| Determine whether the microbiome composition can predict risk for colorectal cancer | Whole genome sequencing and metabolomics will be used to characterize the patient's microbiome. High and low risk subjects will be followed for 8 years to determine if any get CRC. | 2-8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identify correlations between microbiome composition and immune markers | CyTOF and cytokine analysis will be performed on the blood samples to characterize the patient's immune phenotype | 6-12 months | 
| Determine whether the microbiome composition can predict overall survival | Survival and tumor progression will be monitored for an extended time beyond sample collection | 6-24 months | 
| Build a library of samples and data for future research | Samples will be stored and data saved in a HIPAA-compliant database. Samples will be linked to patient metadata. | 6-24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microbiome, immunotherapy, checkpoint inhibitor, cancer, colonoscopy