NCT04670588

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

A Prospective Observational Study to Determine the Feasibility of Tumor Response Assessment by Circulating Tumor DNA in Patients With Locally Advanced Rectal Cancer Undergoing Total Neoadjuvant Therapy

• Status: Withdrawn
• Phase: —
• Study type: Observational
• Enrollment: 0 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Rectal Cancer

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Circulating tumor DNA(ctDNA) level measurement	The ctDNA level will be measured using the Signatera platform developed by Natera, Inc. Signatera is a patient-specific, tumor informed custom-built ctDNA monitoring assay.

Timeline

• Start date: 2021-03-31
• Primary completion: 2022-06-01
• Completion: 2022-06-01
• First posted: 2020-12-17
• Last updated: 2022-07-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated device study