ctDNA-Informed Management for Rectal Cancer

(ULTIMATE Trial)

Overseen By Ankit Sarin, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Disqualifiers: Prior rectal cancer treatment, Metastatic disease, Hemodialysis, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates how well the Signatera Genome ultra-sensitive ctDNA blood test can guide treatment for individuals with early-stage rectal cancer. The goal is to determine if the test can predict who might avoid surgery after initial treatments like chemotherapy and radiation. Participants will either use the blood test to decide on next steps or follow the usual surgery route after treatment. The trial seeks individuals diagnosed with rectal cancer who have already completed specific chemotherapy and radiation treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What prior data suggests that the Signatera Genome ultra-sensitive ctDNA blood test is safe for use in early-stage rectal cancer management?

Previous studies have used the Signatera Genome ultra-sensitive ctDNA blood test to monitor colorectal cancer. This blood test helps predict the potential return of cancer and has been used to check for cancer after surgery.

The test is non-invasive, avoiding surgery or complicated procedures, making it generally safe and easy to manage. Evidence shows no major side effects or risks from the blood test itself.

However, as this is a phase 2 study, researchers continue to gather more information on its effectiveness and overall safety. So far, the Signatera test has been used successfully in other studies for similar purposes without significant safety concerns. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how a cutting-edge blood test, the Signatera ultra-sensitive ctDNA test, might change the way rectal cancer is managed. Unlike traditional approaches that often rely on surgery and chemotherapy, this trial investigates a "Watch and Wait" surveillance strategy, using the blood test to detect tiny fragments of cancer DNA in the bloodstream. This method could potentially help doctors decide if surgery can be safely postponed or even avoided, reducing the patient's exposure to invasive procedures. By focusing on personalized cancer monitoring, this trial aims to offer a more tailored, less invasive approach to managing rectal cancer.

What evidence suggests that this trial's treatments could be effective for rectal cancer?

Research has shown that the Signatera Genome blood test can detect cancer recurrence earlier than traditional methods. In studies with colorectal cancer patients, it has effectively identified small amounts of residual cancer after treatment. One study demonstrated that this test helped identify potential relapses in stage II colon cancer patients, enabling early intervention. By tracking tiny pieces of tumor DNA in the blood, the test offers a more accurate way to monitor cancer. In this trial, participants in the "ctDNA informed management arm" will undergo Watch and Wait surveillance using this test, which may aid in managing early-stage rectal cancer by providing timely information on treatment effectiveness. ^{1 2 3 6 7}

Who Is on the Research Team?

Ankit Sarin, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for individuals with early-stage rectal cancer. Participants must be eligible to undergo total neoadjuvant therapy (TNT). Specific inclusion and exclusion criteria details are not provided, but typically these would involve health status, prior treatments, and other medical conditions.

Inclusion Criteria

Ability to understand and willingness to sign the informed consent form (ICF)

I am 18 years old or older.

My rectal cancer has been confirmed through a tissue test and is available for a specific DNA test.

Exclusion Criteria

Any condition that in the opinion of the investigator would interfere with the participant's safety or compliance while on trial

I have had treatment for rectal cancer before, but not as part of cohort B.

My scans show cancer has spread to distant parts of my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Total Neoadjuvant Therapy (TNT)

Participants receive total neoadjuvant therapy as part of the standard of care

Varies

ctDNA Informed Management

Participants are assigned to either ctDNA informed management (Watchful Waiting) or post TNT SOC surgery based on ctDNA assay results

Up to 2 years

Follow-up

Participants are monitored for ctDNA positivity and disease-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Signatera Genome ultra-sensitive ctDNA blood test

Trial Overview

The study tests if managing treatment based on ctDNA levels using the Signatera Genome assay can improve outcomes in rectal cancer patients compared to standard post-TNT surgery. It measures complete response rates and disease-free survival as main goals.

How Is the Trial Designed?

Group I: ctDNA informed management arm (Watch and Wait surveillance) Experimental Treatment 1 Intervention

Group II: Post TNT SOC surgery arm Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07209215

ctDNA-Informed Management of Early-Stage Rectal Cancer

This is a phase 2 pragmatic study to examine the utility of ctDNA-informed treatment management for participants with early-stage rectal cancer ...

2.

natera.com

natera.com/oncology/signatera-advanced-cancer-detection/

Signatera™ Indications - Circulating Tumor DNA Blood Test

Signatera™ is a sensitive ctDNA test for colorectal cancer that can identify relapse sooner than standard tools. Click here to learn more about it.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12186373/

Circulating tumor DNA for MRD detection in colorectal cancer

This study enrolled 230 patients diagnosed with stage II colon cancer and demonstrated the clinical efficiency of ctDNA MRD using a tumor- ...

4.

trial.medpath.com

trial.medpath.com/clinical-trial/b0b70fbd71fc06ce/nct07209215-ultrasensitive-ctdna-early-stage-rectal-cancer

ctDNA-Informed Management of Early-Stage Rectal Cancer

This is a phase 2 pragmatic study to examine the utility of ctDNA-informed treatment management for participants with early-stage rectal ...

5.

natera.com

natera.com/company/news/signateratm-genome-clinical-performance-highlighted-at-asco-2025/

Signatera™ Genome Clinical Performance Highlighted at ...

The study analyzed the performance of Signatera Genome in a cohort of 392 patients (> 2,600 plasma samples) across five different tumor types ( ...

6.

natera.com

natera.com/resource-library/natera-publications/signatera-publications/

Signatera Publications

Circulating Tumor DNA Detects Minimal Residual Disease in Patients with Locally Advanced Rectal Cancer After Total Neoadjuvant Therapy. Cancers. 2025; 17(15): ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07125729

Study Details | NCT07125729 | Minimal Residual Disease ...

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 ...