Response Assessment by Circulating Tumor DNA in Patients With Locally Advanced Rectal Cancer

Withdrawn

• Conditions: Rectal Cancer
• Interventions: Diagnostic Test: Circulating tumor DNA(ctDNA) level measurement

• Registration Number: NCT04670588
• Lead Sponsor: Medical College of Wisconsin

Brief Summary

This is a single-arm observational study to determine the feasibility of assessing tumor response utilizing Circulating tumor DNA (ctDNA) in patients of with locally advanced rectal cancer (LARC) undergoing standard-of-care total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or modified FOLFIRINOX) followed by concurrent chemoradiation (50.4 Gy over approximately six weeks with concurrent radiosensitizing dose of capecitabine/5-fluorouracil).

Detailed Description

In this observational study, patients with LARC who are selected for the standard-of-care TNT will be enrolled. After obtaining informed consent, a venous blood sample and the archival tissue block from the initial diagnostic rectal tumor biopsy will be sent to the Natera laboratory for designing patient-specific ctDNA assay, which will be used to measure ctDNA levels in the peripheral venous blood samples at various time points coinciding with the standard studies to assess tumor response. The blood sample needed for designing the assay and measuring the baseline ctDNA level will be obtained within four weeks before neoadjuvant chemotherapy begins. Subsequently, for patients undergoing 16 weeks of neoadjuvant chemotherapy, blood samples will be obtained for ctDNA level measurement at three time points ( after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the magnetic resonance imaging (MRI) study, after 16 weeks/8 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery ). For patients who receive eight weeks of neoadjuvant chemotherapy, two blood samples will be obtained for subsequent ctDNA measurements (after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery). All patients may also choose to undergo additional serial ctDNA level measurements for surveillance after the surgery every three to four months for two years (optional).

Tumor response rate assessed by ctDNA (defined as reduction of ctDNA level at least by 90% compared to the baseline level) will be compared with the response rate assessed by the standard method (proctoscopic examination, pelvic MRI, etc.) to explore if a significant correlation exists between these two response assessment methods. If preliminary data support the hypothesis that peripheral blood ctDNA can be utilized for tumor response assessment in this scenario, a larger study will be conducted to validate this method. Once validated, ctDNA measurement can potentially replace expensive, uncomfortable, and time-consuming methods of tumor response assessment like MRI.

Study Timeline

• Study First Submitted: 2020-12-10
• Study First Submitted QC: 2020-12-10
• Study First Posted: 2020-12-17
• Study Start: 2021-03-31
• Primary Completion: 2022-06-01
• Study Completion: 2022-06-01
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-14
• Last Update Posted: 2022-07-18

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Patients with histologically or cytologically documented rectal cancer eligible for total neoadjuvant therapy (TNT).
2. Male or female subjects ≥18 years old.
3. Rectal tumor biopsy is available for SignateraTM assay development for ctDNA measurement.
4. Patients must be able to understand the informed consent form and provide written consent.

Exclusion Criteria

1. Patients without available rectal biopsy tissue for SignateraTM assay development.
2. Patients with rectal cancer not eligible to receive standard-of-care TNT for any reason.
3. Patients with undetectable ctDNA level in the baseline blood sample.
4. Patients without trackable mutation in the rectal tumor.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Locally advanced rectal cancer patients	Circulating tumor DNA(ctDNA) level measurement	Patients with LARC undergoing TNT.

Primary Outcome Measures

Name	Time	Method
Mean serum ctDNA concentration	Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.	This measure is the concentration of ctDNA in plasma expressed as mean tumor molecules (MTM)/ml at specific time points.

Secondary Outcome Measures

Name	Time	Method
Response based on standard clinical assessments	Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.]	This measure is the number of subjects achieving a clinical change of tumor size based on standard clinical assessments. Response will be a determined as a subjective measure by experienced clinicians using any combination of pelvic MRI, visual proctoscopic examination, sigmoidoscopy, and/or endoscopic ultrasound.
Response based on serum ctDNA level (change from baseline)	Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery	This measure is the number of subjects achieving a reduction of ctDNA level (mean tumor molecules\[MTM\]/ml) by \> 90% compared to the baseline.

Trial Locations

Locations (1)

Froedtert & the Medical College of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States