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

City of Hope

Status: Enrolling

Conditions: Stage IV Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Resectable Colorectal Carcinoma; Stage III Colorectal Cancer AJCC v8

Treatments: Procedure: Biospecimen Collection; Other: Electronic Health Record Review; Other: cfDNA or ctDNA Measurement

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07125729

NCI-2025-05428 (Registry Identifier)

P30CA033572 (U.S. NIH Grant/Contract)

24372 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 1 patient group

Screening (Haystack MRD, Signatera)

Experimental group

Description:

Patients undergo archival tissue and blood sample collection and Haystack MRD and Signatera ctDNA/cfDNA testing prior 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.

Treatment:

Other: Electronic Health Record Review

Other: cfDNA or ctDNA Measurement

Procedure: Biospecimen Collection