ctDNA and Organ Preservation/Pathologic CR in Rectal Cancer

Study Overview
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Brief Summary
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This prospective observational, non-therapeutic study for patients with T3, T4, or node positive rectal cancer eligible to undergo total neoadjuvant therapy. This research study involves the collection of data and biospecimens (blood and tissue) to see if the presence of circulating tumor DNA (genetic material) ctDNA will help monitor rectal cancer more closely and potentially detect a recurrence before routine scans, performed per standard of care C2i Genomics, a biotechnology company, and the Spier Foundation are supporting this research study by providing funding for the study.

Detailed Description
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The research study procedures include screening for eligibility and the collection of data and biospecimens. Non-operative management is offered as part of routine clinical care. It is expected that up to 60 participants will be enrolled, with the goal that 55 participants will take part in this research study . Participants enrolled on the study will remain on study for up to 60 months.

Official Title
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A Study of the Role of Circulating Tumor DNA in Predicting the Likelihood of Organ Preservation or Pathologic Complete Response After Neoadjuvant Therapy for Rectal Cancer

Conditions
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Rectal Cancer, Non Metastatic Rectal Cancer

Intervention / Treatment
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* Other: ctDNA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with T3, T4, or node-positive non-metastatic rectal cancer. Participants must have original tumor tissue (formalin-fixed, paraffin embedded specimens) available for analysis or be willing to undergo a baseline research biopsy. Participants must be 18 years of age or older. ECOG 0-2. Participants must be eligible for at least 3 months of FOLFOX, FOLFIRINOX/FOLFOXIRI, or CAPOX Participants must be eligible for long course chemoradiation to 40-54 Gy. Participants must be able to understand and willing to sign a written informed consent document. Exclusion Criteria: Participants must not have any other organ cancer evident at the time of enrollment. Participants may not have any other concurrent serious illness that makes participation on this study impractical or clinically inappropriate. Participants must not be actively or planning to be pregnant or breastfeeding

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 |
| --- | --- |
| EVALUATION OF CTDNA<br>This prospective observational, non-therapeutic study will enroll patients with T3, T4, or node positive rectal cancer eligible to undergo total neoadjuvant therapy/ All procedures involved with this trial will be done as per standard of care - Except for the initial research biopsy, quality of life assessments and ctDNA collection | Other: ctDNA<br>* initial research biopsy, quality of life assessments and ctDNA collection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of successful non-operative management |  | 1 year | 
| Rate of successful pathologic complete response |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of local recurrence | Local recurrence is defined as cancer coming back is in the same place as the original cancer or very close to it. Local recurrence will be assessed in participants who achieved a Clinical Complete Response (cCR) or Near Complete Clinical Response (nCR) after rectal cancer treatment by ctDNA status with the C2i assay. | 5 years | 
| EORTC-QLQ-CR 29 questionnaire | European Organization for Research and Treatment of Cancer-Colorectal surgery (EORTC-QLQ-CR 29) is a 29-item patient-reported questionnaire to assess health-related quality of life in patients with colorectal cancer. Each question ranges in score from 1 to 4. Higher scores indicate higher levels of symptoms or less functioning. | Up to 30 months | 
| FACT-C questionnaire | Functional Assessment of Cancer Therapy- Colorectal (FACT-C) is a 37-item patient-reported questionnaire to assess quality of life in patients with colorectal. FACT-C questions are divided into four primary quality of life domains: Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Participants rate each item on the questionnaire from 0 to 4. Total score range is from 0 to 136. Higher scores generally indicate better quality of life. | Up to 30 months | 
| IADL Scale | Instrumental Activities of Daily Living (IADL) Scale is an 8-item patient-reported questionnaire with a summary score from 0 (low function) to 8 (high function). IADLs are things you do every day to independently take care of yourself and your home. | Up to 30 months | 
| Brief Pain Inventory (BPI) questionnaire | Brief Pain Inventory (BPI) is a questionnaire to measure the severity and interference of pain on daily functions in participants with cancer. BPI scale total score: worst pain score: 1-4 = mild pain worst pain score: 5-6 = moderate pain worst pain score: 7-10 = severe pain | Up to 30 months | 
| Bowel function assessment with LARS score | Low Anterior Resection Syndrome (LARS) score (LARS) is a 5-item questionnaire to assess bowel dysfunction following a low anterior resection for rectal cancer. LARS total score: 0-20 = no dysfunction 21-29 = minor dysfunction 30-42 = major dysfunction | Up to 30 months | 
| Bowel function assessment with FISI score | Fecal Incontinence Severity Index (FISI) is a patient-reported questionnaire that helps quantify the impact of adult incontinence leakage on quality of life. Total score range is from 0 to 61. Higher scores indicate a higher perceived severity of fecal incontinence and related impact on quality of life. | Up to 30 months | 
| Bowel function assessment with FIQOL score | Fecal Incontinence Quality of Life (FIQOL) is a 29-item patient-reported questionnaire to assess quality of life of participants with fecal incontinence. The questionnaire has 4 subscales: lifestyle, coping/behavior, depression/self-perception and embarrassment. Subscale scores range from 1 to 5 and are the average response to all items on each scale. Total FIQOL score is the sum of all four subscales. Lower scores indicate lower functional status and related quality of life. | Up to 30 months | 
| Disease-free survival (DFS) | Disease-free survival (DFS) is defined as the length of time after completion of rectal cancer treatment that the patient survives without any signs or symptoms of that cancer. | Up to 30 months | 
| Overall Survival (OS) | Overall survival (OS) is defined as the length of time after starting rectal cancer treatment that participants are still alive. | Up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rectal Cancer, Non Metastatic Rectal Cancer