CIRCULATE-US: Trial overview

CIRCULATE-US is a phase II/III clinical trial studying whether chemotherapy is recommended — and if so, what kind of chemotherapy — for stage II and III colon cancer patients, depending on the presence or absence of circulating tumor DNA (ctDNA) after surgery.

Here’s some background info

Let’s take a look at the standard treatment for early-stage (II and III) colon cancer. The current treatment strategy is:

1. Surgery to remove the part of the colon containing the tumor, then
2. Clean-up (also called adjuvant) chemotherapy after surgery

For stage III patients:

Out of 100 patients diagnosed with stage III colon cancer, about 50 of them are cured with surgery alone. Of the remaining 50, about 25 are cured with surgery and adjuvant chemotherapy, and the other 25 will progress to stage IV.

However, all stage III colon cancer patients get the same thing — surgery and adjuvant chemotherapy. This is because so far, we haven’t had a test to tell us whether or not a patient’s cancer is likely to come back after surgery. With the advent of ctDNA testing, we may have such a test.

This trial looks at some of the questions this new information raises, including:

• If a person is ctDNA positive after surgery, can chemotherapy clear ctDNA?
• Is a stronger chemo regimen, with a longer duration of treatment, better at preventing ctDNA from showing up?
• How does ctDNA status relate to cancer recurrence and overall survival?
• Will treating ctDNA-positive patients with aggressive treatment early on change their outcomes, or will they progress to stage IV regardless?
• If patients are ctDNA negative after surgery, are they part of the 50% of patients already cured by surgery? If so, does this group really need clean-up chemotherapy?

For stage II patients:

Stage II colon cancer is most commonly treated with surgery alone. Only a small subset of stage II patients receive adjuvant chemotherapy, if their tumor has characteristics that signal aggressive disease. CtDNA testing may provide additional information to help identify the patients who would benefit most from chemotherapy.

This trial looks at some of the questions this new information raises, including:

• In stage II patients who are ctDNA positive, does the type and duration of chemotherapy affect cancer recurrence and overall survival?

In simple terms:

All early-stage colon cancer patients receive the same treatment — surgery and chemotherapy. Some patients don’t need chemo and would be cured by surgery alone. For others, their chemotherapy regimen is appropriate for them. For another group of patients, the standard chemo (FOLFOX/CAPOX) is not strong enough, and isn’t effective at preventing recurrence.

CtDNA tests could be a way to figure out which groups patients fall into: Those who should skip chemo, get standard chemo, or a stronger type of chemo. This is what this study is hoping to find out.

The cost of ctDNA testing and other treatments done as part of the trial will be covered by the trial. 

The trial has four study groups. After surgery, participants will be tested for the presence or absence of ctDNA. If positive, patients will randomly receive either FOLFOX/CAPOX (5-fluorouracil, leucovorin and oxaliplatin OR capecitabine and oxaliplatin) or FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin and irinotecan). If negative, patients will randomly receive either FOLFOX/CAPOX or regular surveillance without chemotherapy. If a participant later tests positive for ctDNA, they will be randomized into the FOLFOX/CAPOX or FOLFOXIRI groups.

Who is the trial for?

The CIRCULATE-US study is currently enrolling adults diagnosed with stage II or III colon cancer that has been previously treated with surgery. Patients must not have received prior systemic therapy, such as chemotherapy.

If you fall into the criteria listed above, want your treatment to be more personalized, and are interested in using ctDNA to guide chemotherapy decisions, this trial may be a good fit for you. 

Interested? Here are the details

Phase: II/III

Clinicaltrials.gov ID number: NCT05174169

Trial sponsors: The National Cancer Institute (NCI), NRG Oncology, and Natera

If you want to learn more about this trial from the Principal Investigator, Dr. Christopher Lieu, don’t forget to check out this DocTalk.