A Study of the Role of Circulating Tumor DNA in Predicting the Likelihood of Organ Preservation After Clinical Complete Response to Neoadjuvant Therapy for Rectal Cancer

Study Overview
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Brief Summary
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In this research study, the investigators are looking to see if the circulating tumor DNA (genetic material), also known as ctDNA, in the blood will help them predict whether the participant's cancer will come back.

Detailed Description
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In this research study, the investigator are performing blood draws to see if the presence or absence of circulating tumor DNA (ctDNA), the genetic material in the participant's cancer's cells, will help the investigators predict whether the participant's cancer will come back or not.

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

Conditions
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Gastrointestinal Malignancies

Intervention / Treatment
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* Other: The Functional Assessment of Cancer Therapy- Colorectal


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have achieved a clinical complete response (cCR) within 3 months of last therapy - defined as absence of residual ulceration, mass or mucosal irregularity at endoscopic assessment - following neoadjuvant therapy with chemoradiation or chemotherapy followed by radiation for stage I, II, or III non-metastatic rectal cancer. (Whitening of the mucosa with presence of telangiectasia will be accepted as cCR.) Participants must have original tumor tissue (formalin-fixed, paraffin-embedded specimens) available for analysis Participants must be 18 years of age or older. Participants must be able to understand and willing to sign a written informed consent document. Participants must have received long course chemoradiation to 40-54 Gy. Participants must have received at least 4 cycles of FOLFOX Participant must be no more than 3 months past the conclusion of initial chemoradiation of rectal cancer (i.e., end of chemoradiation). Exclusion Criteria: Participants may 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Tumor Sequencing<br>Quality of life assessments will be collected using The Functional Assessment of Cancer Therapy- Colorectal Blood for circulating tumor DNA will be collected | Other: The Functional Assessment of Cancer Therapy- Colorectal<br>* The Functional Assessment of Cancer Therapy- Colorectal (FACT-C) questionnaire measures health-related quality of life for people with chronic illnesses.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| One year local recurrence rate in participants that test positive for ctDNA compared to participants that tested negative for ctDNA | Local recurrence will be defined as recurrence of the pathologically confirmed adenocarcinoma. This may be detected by endoscopy for intraluminal recurrence or after radical surgery for radiographic evidence of extraluminal/mesorectal recurrence. The recurrence must be in the peri-anastomic site or rectal stump, or pre-sacral area. Regional nodal recurrence and lateral pelvic lymph node recurrence of rectal cancer are also included in this definition. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local recurrence rate at any time up to 5 years in patients who have achieved a clinical complete response after rectal cancer treatment but who test positive for circulating tumor DNA at study entry | Local recurrence will be defined as recurrence of the pathologically confirmed adenocarcinoma. This may be detected by endoscopy for intraluminal recurrence or after radical surgery for radiographic evidence of extraluminal/mesorectal recurrence. The recurrence must be in the peri-anastomic site or rectal stump, or pre-sacral area. Regional nodal recurrence and lateral pelvic lymph node recurrence of rectal cancer are also included in this definition. | 5 years | 
| Overall rate of local recurrence by stratified KRAS/BRAF status and possibly other gene targets | Local recurrence will be defined as recurrence of the pathologically confirmed adenocarcinoma. This may be detected by endoscopy for intraluminal recurrence or after radical surgery for radiographic evidence of extraluminal/mesorectal recurrence. The recurrence must be in the peri-anastomic site or rectal stump, or pre-sacral area. Regional nodal recurrence and lateral pelvic lymph node recurrence of rectal cancer are also included in this definition. | 5 years | 
| Median EORTC QLQ-CR29 Score | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) for Colorectal cancer(CR) 29 item questionnaire. The survey will be given at baseline, 6, 12, and 24 months. Results will be reported as the median score for each question. A score of 1 represents 'Not at All' and 4 represents 'Very Much'. | Baseline, 6 months, 12 months, 24 months | 
| Median SF-12 Health Survey Score | The SF-12 is a 12 item validated questionnaire that assesses a participants view of their health. Scores will be normalized on a 100 point scale with higher scores representing better health. | Baseline, 6 months, 12 months, 24 months | 
| Median LARS Score | The Low Anterior Resection Syndrome (LARS) Score is used to assess bowel dysfunction. The survey is assessed on a scale of 0-42 points, with a higher score indicating worse bowel dysfunction. | Baseline, 6 months, 12 months, 24 months | 
| Median FIQOL Score | Fecal Incontinence Quality of Life (FIQOL) Score. Lower scores represent lower functional status. | Baseline, 6 months, 12 months, 24 months | 
| Median Fecal Incontinence Severity Index (FISI) score | The FISI measures incontinence for gas, mucus, liquid stool,and solid stool. The survey assesses the number of times per day that the participant experiences incontinence for gas, mucus, liquid stool,and solid stool. Higher scores represent a higher degree of fecal incontinence. | Baseline, 6 months, 12 months, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastrointestinal Malignancies