Resectable Colorectal Carcinoma, Stage II Colorectal Cancer AJCC v8, Stage III Colorectal Cancer AJCC v8, Stage IV Colorectal Cancer AJCC v8
Conditions
Brief summary
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
PROCEDUREBiospecimen Collection
Undergo archival tissue and/or blood sample collection
Undergo Haystack MRD and Signatera ctDNA/cfDNA testing
OTHERElectronic Health Record Review
Ancillary studies
Sponsors
City of Hope Medical Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal residual disease (MRD) rate with Haystack and Signatera® | Up to 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time interval of detection of disease recurrence by Haystack test, radiological imaging, and Signatera test | Up to 5 years | 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. |
| Level of association of circulating tumor deoxyribonucleic acid (ctDNA) result and status of recurrence and non-recurrence | Up to 5 years | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMarwan G Fakih
City of Hope Medical Center
Outcome results
None listed