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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stage IV Colorectal Cancer AJCC v8; Stage III Colorectal Cancer AJCC v8; Stage II Colorectal Cancer AJCC v8; Resectable Colorectal Carcinoma
• Intervention / Treatment: Other: Electronic Health Record Review; Procedure: Biospecimen Collection; Other: cfDNA or ctDNA Measurement

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Recruiting
      • CTCA at Western Regional Medical Center
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
  • California
    • Corona, California, United States, 92882
      • Recruiting
      • City of Hope Corona
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Huntington Beach, California, United States, 92648
      • Recruiting
      • City of Hope Seacliff
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Irvine, California, United States, 92618
      • Recruiting
      • City of Hope at Irvine Lennar
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Lancaster, California, United States, 93534
      • Recruiting
      • City of Hope Antelope Valley
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Long Beach, California, United States, 90813
      • Recruiting
      • City of Hope at Long Beach Elm
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Newport Beach, California, United States, 92660
      • Recruiting
      • City of Hope at Newport Beach Fashion Island
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • South Pasadena, California, United States, 91030
      • Recruiting
      • City of Hope South Pasadena
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Torrance, California, United States, 90503
      • Recruiting
      • City of Hope South Bay
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
    • Upland, California, United States, 91786
      • Recruiting
      • City of Hope Upland
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Recruiting
      • City of Hope Atlanta Cancer Center
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org
  • Illinois
    • Zion, Illinois, United States, 60099
      • Recruiting
      • City of Hope at Chicago
      • Principal Investigator: Marwan G. Fakih
      • Contact: Marwan G. Fakih; Phone Number: 626-613-5025; Email: mfakih@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Screening (Haystack MRD, Signatera); 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.

Other: Electronic Health Record Review; Ancillary studies; Procedure: Biospecimen Collection; Undergo archival tissue and/or blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Other: cfDNA or ctDNA Measurement; Undergo Haystack MRD and Signatera ctDNA/cfDNA testing; Other Names: Cell-Free DNA/Circulating Tumor DNA Measurement; cfDNA/ctdDNA Measurement; cfDNA/ctDNA; cfDNA/ctDNA Measurement; Circulating Cell-Free DNA/Circulating Tumor-Derived DNA Measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimal residual disease (MRD) rate with Haystack and Signatera®	Will assess the MRD rate with Haystack (positive circulating tumor deoxyribonucleic acid [+ctDNA] and negative imaging) versus MRD rate with Signatera (+ctDNA and negative imaging). Sensitivity (i.e., true positive rate - proportion of patients who recur that are found to be MRD positive), specificity (i.e., true negative rate - proportion of patients who do NOT recur that are found to be MRD negative), positive predictive value (i.e., proportion of positive tests which are true positives) and negative predictive value (proportion of negative tests which are true negatives) of the Haystack test and of the Signatera test for predicting disease recurrence will be calculated and summarized at various times of testing.	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time interval of detection of disease recurrence by Haystack test, radiological imaging, and Signatera test	The time interval between recurrence detection by the Haystack MRD test compared to radiological imaging assessment and Signatera test will be calculated as the time interval between the detection of disease recurrence by each of the methods (Haystack test, radiological imaging, Signatera test). Lead-time will be estimated by means of appropriate formulas and Monte Carlo simulation. Pairwise comparisons of detection times will be performed using the log-rank test. Cox proportional hazards model will be used to estimate the hazard ratios and 95% confidence intervals for each detection method.	Up to 5 years
Level of association of circulating tumor deoxyribonucleic acid (ctDNA) result and status of recurrence and non-recurrence	Logistic regression model will be used to estimate the level of association of ctDNA result and the status of recurrence and non- recurrence in patients with resectable stage II-IV colorectal cancer. Multivariable models adjusting for relevant clinical variables will be evaluated to assess the importance of these prognostic factors and support the robustness of ctDNA findings.	Up to 5 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Marwan G Fakih, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2025
• Primary Completion (Estimated): January 9, 2028
• Study Completion (Estimated): January 9, 2028

Study Registration Dates

• First Submitted: August 10, 2025
• First Submitted That Met QC Criteria: August 10, 2025
• First Posted (Estimated): August 15, 2025

Study Record Updates

• Last Update Posted (Estimated): August 15, 2025
• Last Update Submitted That Met QC Criteria: August 10, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 24372 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2025-05428 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No