Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

Colorectal Cancer Clinical Trial

Official title:

Circulating Tumor DNA to Monitor the Efficacy of Total Neoadjuvant Therapy for Rectal Cancer

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05356585
• Other study ID #: CASE9221
• Status: Withdrawn
• Start date: December 30, 2023
• Est. completion date: June 30, 2024

Study information

• Verified date: April 2024
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to use the SignateraTm assay created from rectal tumor biopsies to monitor participants' blood for fragments of DNA shed by tumor cells. The tumor DNA fragments are referred to as circulating tumor DNA, or ctDNA for short.

Description:

Rectal cancer tissue samples that were collected from participants' previous biopsies will be sent to Natera for Signatera assay creation after enrollment onto the study.

One 6 mL tube of blood will be obtained at baseline prior to initiation of treatment. Blood will also be obtained in two 6 tubes at the following points: 3-4 weeks into chemoradiation therapy (CRT), after CRT, after chemotherapy, after surgery for those who undergo resection, and during surveillance 3 months after surgery or at the end of treatment for one year after completion of TNT (total neoadjuvant therapy).

The primary objective of the study is to estimate the percentage of patients with positive ctDNA at the end of TNT .

The secondary objectives of the study include:

1. Estimating the change in ctDNA after chemoradiation and chemotherapy

2. Characterize the correlation of complete response to TNT with presence or absence of ctDNA

3. Describe the recurrence rate in participants with and without ctDNA after TNT

4. Characterize the correlation of ctDNA at end of TNT with recurrence free survival at 2 years.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 30, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Newly histologically documented rectal adenocarcinoma or biopsy-proven adenoma with MRI rectum and CT chest/abdomen or PET/CT imaging consistent with stage II or III disease

• Plan is for participant to undergo standard TNT with induction chemoradiation

• Age = 18 years of age

Exclusion Criteria:

• Stage I, recurrent, or metastatic rectal cancer

• Received prior therapy for this rectal cancer

• No baseline tumor biopsies with adenocarcinoma or adequate amount of tissue from biopsies available to send for SignateraTM assay development

Related Conditions & MeSH terms

• Colorectal Cancer
• Rectal Cancer
• Rectal Neoplasms

Intervention

Genetic:
• SignateraTM assay
A customized tumor-informed ctDNA test that, after receiving the tumor tissue, examines whole exome sequencing of a biopsied tumor to find the somatic tumor-derived mutations. From those mutations, the 16 most clonal mutations are used to create a personal assay

Locations

Country	Name	City	State
United States	Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The recurrence rate (local and distant) with positive ctDNA and negative ctDNA after TNT	The recurrence rate (local and distant) is the number of participants with positive ctDNA and negative ctDNA after TNT for both participants who undergo watch and wait and those who have surgery. Non operative management (watch and wait) is offered to participants who have a complete clinical response who will comply with required surveillance. Outcomes will be recorded and described for all participants, those who underwent surgery and those who underwent non-operative management.	Up to 24 months after TNT
Other	The correlation of ctDNA at end of TNT with relapse-free survival	The presence or absence of ctDNA with relapse-free survival.Time to event variable will be summarized using the Kaplan-Meier method. Outcomes will be recorded and described for all patients, those who underwent surgery and those who underwent non-operative management.	After 2 years of surveillance post-TNT
Primary	Detectable ctDNA at the Completion of TNT	The percentage of participants with detectable ctDNA at the completion of TNT	up to 24 months after TNT
Secondary	Change in ctDNA	The change in ctDNA (continuous and categorical positive/negative) during and at the end of neoadjuvant chemoradiation and with chemotherapy will be measured. Continuous measurements will be summarized using medians and ranges. Categorical factors will be summarized using frequencies and percentages. Changes in ctDNA will be analyzed by using the Mann-Whitney U test or the Fisher's exact test for continuous or categorical variables, respectively.	up to 24 months after TNT
Secondary	Correlation of Complete Response TNT	Correlation of complete response to TNT defined by presence or absence of ctDNA.	Up to 24 months after TNT