Minimal Residual Disease Testing for the Early Detection of Cancer Recurrence in Resectable Stage II-IV Colorectal Cancer Patients

Official title

ctDNA Testing in Resectable Stage II-IV Colorectal Cancer Patients: A Head-to-Head Performance Comparison

Overview

This clinical trial compares minimal residual disease (MRD) testing with the Haystack blood test (assay) to the Signatera® assay for the early detection of the cancer returning (cancer recurrence) in patients with stage II-IV colorectal cancer (CRC) that can be removed by surgery (resectable). MRD testing looks for evidence of remaining tumor following treatment that is only apparent using highly sensitive techniques. There are few effective tools available outside of imaging to identify CRC patients with MRD who may be at the highest risk for cancer recurrence after surgery. Early detection of CRC recurrence after surgery is important, as it may increase the chance of curative (ability to cure) outcomes for patients with cancer recurrence. Currently, the Signatera assay is used to monitor whether CRC recurs after surgery, however it is not a very sensitive test. Early work with the Haystack assay suggests it may be more sensitive than the Signatera assay, which may be more effective for the early detection of cancer recurrence in patients with resectable stage II-IV CRC.

Detailed description

PRIMARY OBJECTIVE:

I. To compare the clinical performance of the Haystack MRD test and the Signatera® test in patients with stage II-IV CRC patients treated with curative intent surgery with or without adjuvant therapy.

SECONDARY OBJECTIVE:

I. To calculate the lead time (months) of recurrence detection by the Haystack MRD test in curatively resected colorectal cancer patients to 1) radiological recurrence time 2) Signatera® test positivity.

EXPLORATORY OBJECTIVE:

I. To explore the performance of up to two cancer detection assays (BestSEEK and enACT) in development by Dr. Tomasetti at City of Hope - Translational Genomics Research Institute (TGen) and City of Hope.

OUTLINE:

Patients undergo archival tissue and blood sample collection and Haystack MRD and Signatera circulating tumor deoxyribonucleic acid (ctDNA)/cell-free deoxyribonucleic acid (cfDNA) testing prior to standard of care (SOC) surgical resection. Patients then undergo blood sample collection and Haystack MRD and Signatera ctDNA/cfDNA testing 3-10 weeks after surgery, every 3 months for 2 years post-surgery, and then every 6 months for years 3-5 post-surgery in the absence of disease progression.

Interventions

• Procedure Biospecimen Collection
  Undergo archival tissue and/or blood sample collection
• Other cfDNA or ctDNA Measurement
  Undergo Haystack MRD and Signatera ctDNA/cfDNA testing
• Other Electronic Health Record Review
  Ancillary studies

Primary outcome measures

• Minimal residual disease (MRD) rate with Haystack and Signatera® [Time frame: Up to 5 years]

Secondary outcome measures (2)

• Time interval of detection of disease recurrence by Haystack test, radiological imaging, and Signatera test [Time frame: Up to 5 years]
• Level of association of circulating tumor deoxyribonucleic acid (ctDNA) result and status of recurrence and non-recurrence [Time frame: Up to 5 years]

Eligibility criteria

Inclusion criteria

• Documented written informed consent of the participant
• Age: ≥ 18 years
• Diagnosis of stage II, III or IV colorectal cancer (any gender) if enrolled post-operatively. If a treatment naïve patient is enrolled pre-operatively and determined to be pathological stage I, the patient will be replaced
• Patient who are to undergo a curative intent surgery or have undergone a curative resection and are presenting for surveillance
• Patient identified as an appropriate candidate for Signatera® testing as a standard of care MRD surveillance assay
• Patient willingness to continue Signatera® assay every 3 months for 2 years in the first 2 years after resection and every 6 months for years 3, 4, 5 after resection, as performed by standard of care testing. In addition, the patients should be willing to provide blood samples for Haystack MRD testing at the same intervals of Signatera®, along with willingness to allow access to archival tissue to allow for Haystack MRD assay personalization. Surveillance with ctDNA should be initiated between 3 to 10 weeks from surgery
• Adequate availability of archival tissue or anticipated pathological viable tissue. All untreated primary resection would be expected to have adequate tissue. Patients with resected metastatic disease should have either previously resected primary that is amenable for tumor informed MRD testing or should have adequate archival metastasectomy samples
• Patients with total neoadjuvant therapy (TNT) for rectal cancer and complete clinical response with plans of watchful waiting may also be enrolled as long as there is adequate tissue from prior endoscopic biopsies to allow for Signatera® and Haystack MRD assays

Exclusion criteria

• Inability to safely provide sequential blood samples
• Clinical evidence of unresected metastatic disease
• Inability to give informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Screening

Study locations

United States · 13 centers

• CTCA at Western Regional Medical Center — Goodyear
• City of Hope Corona — Corona
• City of Hope Comprehensive Cancer Center — Duarte
• City of Hope Seacliff — Huntington Beach
• City of Hope at Irvine Lennar — Irvine
• City of Hope Antelope Valley — Lancaster
• City of Hope at Long Beach Elm — Long Beach
• City of Hope at Newport Beach Fashion Island — Newport Beach
• … and 5 more centers

Identifiers

NCT: NCT07125729 · 24372 · NCI-2025-05428 · 24372 · P30CA033572

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗