Colorectal CancerPhase 3CIRCULATEIIINCT07340567
Personalizing Chemotherapy Selection After Surgery for Patients With Stage III Colorectal Cancer Using a Blood Test
A Phase 3 study testing Capecitabine, Oxaliplatin and Folfirinox in people with Colorectal Cancer, run by UNICANCER at 5 sites in 2 countries.
Trial summary
CIRCULATE-III is an international, multicenter, open-label, randomized phase III trial designed to use ctDNA as a selection criterion for intensification or de-escalation of adjuvant chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Capecitabine, Oxaliplatin and Folfirinox
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2,450 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 20 Jul 2026to 1 Nov 2035
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
- Age ≥18 years and <80 years (for patients aged >70 years: G8 geriatric questionnaire score>14)
- Histologically confirmed stage III pMMR/MSS colon and high rectum adenocarcinoma (T, N1 or N2, M0) excluding medium and low rectal cancers (≥12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery are still eligible), without gross or microscopic evidence of residual disease after surgery with curative intent.
- No metastatic disease on CT-Scan and/or liver MRI done within 2 months before inclusion
- Inclusion planned between 10 days to 6 weeks after surgery
- ECOG performance status 0-1 (fit to receive FOLFIRINOX therapy)
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- No prior chemotherapy for CRC
- No prior abdominal or pelvic irradiation for CRC
- Adequate hematological function: neutrophils ≥1,500 /mm3, platelet count ≥100,000/mm3, hemoglobin ≥9 g/dL (5,6 mmol/L)
- Total bilirubin ≤1.5 x ULN (upper limit of normal)
- ASAT and ALAT ≤2.5 x ULN
- Alkaline phosphatase ≤2.5 x ULN
- Serum creatinine ≤120 μmol/L or creatinine clearance ≥50 mL/min according to Modification of Diet in Renal Disease (MDRD) formulae
- Tumor tissue available at baseline
- Women of childbearing potential must have negative serum pregnancy test done within 7 days before the start of study treatment
- Men and women of childbearing potential must agree to use adequate contraception methods for the duration of study treatment and for 6 months after treatment discontinuation
- Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures
- Patient must be affiliated to a social security system (or equivalent) or according to local regulatory requirements
Who cannot join
- Peripheral neuropathy grade ≥1
- Patients who have received neo-adjuvant treatment.
- Comorbidity influencing the 3-year patients' survival including clinically relevant cardiovascular disease, such as Ischemic myocardial infarction in the last year and/or unstable ischemic cardiopathy
- Contra-indication to chemotherapy (inadequate bone marrow, hepatic, renal functions, hypersensitivity to one of the treatments or any of the excipients)
- Patient must not have received bone marrow transplant
- Patient must not have received blood transfusion within 3 months before inclusion
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- Participation in another therapeutic trial
- Partial or complete dihydropyrimidine deshydrogenase (DPD) deficiency.
- MSI/dMMR tumors
- Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥ 5 years.
- Pregnant or breastfeeding women.
- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial social or psychological reasons
- Persons deprived of their liberty or under protective custody or guardianship.
Trial locations and contacts
5 sites in 2 countries.
5 sites in 2 countries
Sweden4 sites
Sahlgrenska University Hospital
Gothenburg, 41345
Skäne University Hospital
Lund, 22185
Södersjukhuset
Stockholm, 11883
Onkologikliniken
Uppsala, 75185
About this study
Official title: Tailoring the Decision for Adjuvant Chemotherapy Using Circulating Tumour DNA, in Patients With Stage III Colorectal Cancer
CIRCULATE-III is an international, multicenter, open-label, randomized phase III trial designed to use ctDNA as a selection criterion for intensification or de-escalation of adjuvant chemotherapy. Eligible patients are randomly assigned to the following treatment groups:
- Patients who test negative for ctDNA receive either capecitabine for 6 months (experimental group) or oxaliplatin + capecitabine for 3 months (standard group).
- Patients who test positive for ctDNA receive either FOLFIRINOX for 6 months (experimental group) or FOLFOX for 6 months (standard group).
Patient participation in the trial will not exceed 66 months after randomization, including a maximum treatment duration of 6 months and a follow-up period of 60 months.
- Conditions
- Colorectal Cancer
- Being tested
- Capecitabine, Oxaliplatin, Folfirinox, FOLFOX regimen
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
De-escalation treatment (capecitabine [CAPE] for 6 months). Or Standard treatment (CAPOX for 3 months)
OxaliplatinDrug
Standard treatment (CAPOX for 3 months)
FolfirinoxDrug
Escalation treatment (5FU + irinotecan + oxaliplatin [FOLFIRINOX] for 6 months)
FOLFOX regimenDrug
Standard treatment (FOLFOX for 6 months)
| Study group | Role | What they receive |
|---|---|---|
| ctDNA-negative cohort : Capecitabine alone | Experimental | ctDNA-negative patients will be included and randomized to de-escalation treatment (capecitabine [CAPE] for 6 months). Receives: Drug: Capecitabine |
| ctDNA-negative cohort : Capecitabine + oxaliplatin | Active comparator | ctDNA-negative patients will be included and randomized to standard treatment (CAPOX for 3 months). Receives: Drug: Capecitabine; Drug: Oxaliplatin |
| ctDNA-positive cohort : FOLFIRINOX | Experimental | ctDNA-positive patients will be randomized to escalation treatment (5FU + irinotecan + oxaliplatin [FOLFIRINOX] for 6 months). Receives: Drug: Folfirinox |
| ctDNA-positive cohort : FOLFOX | Active comparator | ctDNA-positive patients will be randomized to standard treatment (FOLFOX for 6 months). Receives: Drug: FOLFOX regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-inferiority of 6-month CAPE vs 3-month CAPOX ACT in terms of 3-year Disease Free Survival ctDNA-negative cohort
ctDNA-negative cohort: The primary objective is to evaluate the non-inferiority of 6-month capecitabine alone (CAPE; de-escalation strategy) compared to 3-month capecitabine + oxaliplatin (CAPOX; standard therapy) in terms of 3-year disease-free survival (DFS) as adjuvant chemotherapy (ACT) protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-negative.
Measured: DFS will be defined as time from date of randomization until the date of first documented recurrence local or metastatic, date of second colorectal cancer, or date of death from any cause wichever came first, assessed up to 42 months.
Superiority of 6-month FOLFIRINOX vs 6-month FOLFOX ACT in terms of 3-year Disease Free Survival ctDNA-positive cohort
ctDNA-positive cohort: The primary objective is to evaluate the superiority of 6-month FOLFIRINOX (escalation strategy) compared to 6-month FOLFOX (standard therapy) in terms of 3-year DFS as an ACT protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-positive.
Measured: DFS will be defined as time from date of randomization until the date of first documented recurrence local or metastatic, date of second colorectal cancer, or date of death from any cause, wichever came first, assessed up to 42 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2026
- Study start20 Jul 2026
- Primary completion1 Nov 2032 (estimated)
- Study completion1 Nov 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by UNICANCERThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Collaborators
- Natera, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07340567
- Sponsor's protocol ID
- UC-GIG-2410
- Acronym
- CIRCULATEIII
- Status last verified
- Dec 2025
- First submitted
- 18 Dec 2025
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tailoring the Decision for Adjuvant Chemotherapy Using Circulating Tumour DNA, in Patients With Stage III Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07340567
- Acronym / sponsor ID
- CIRCULATEIII / UC-GIG-2410
- Conditions
- Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2,450 participants (estimated)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Collaborators
- Natera, Inc.
- Study start
- 20 Jul 2026 (actual)
- Primary completion
- 1 Nov 2032 (estimated)
- Study completion
- 1 Nov 2035 (estimated)
- First posted
- 14 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
CIRCULATE-III is an international, multicenter, open-label, randomized phase III trial designed to use ctDNA as a selection criterion for intensification or de-escalation of adjuvant chemotherapy. Eligible patients are randomly assigned to the following treatment groups:
- Patients who test negative for ctDNA receive either capecitabine for 6 months (experimental group) or oxaliplatin + capecitabine for 3 months (standard group).
- Patients who test positive for ctDNA receive either FOLFIRINOX for 6 months (experimental group) or FOLFOX for 6 months (standard group).
Patient participation in the trial will not exceed 66 months after randomization, including a maximum treatment duration of 6 months and a follow-up period of 60 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ctDNA-negative cohort : Capecitabine alone | Experimental | Drug: CapecitabinectDNA-negative patients will be included and randomized to de-escalation treatment (capecitabine [CAPE] for 6 months). |
| ctDNA-negative cohort : Capecitabine + oxaliplatin | Active comparator | Drug: Capecitabine, Drug: OxaliplatinctDNA-negative patients will be included and randomized to standard treatment (CAPOX for 3 months). |
| ctDNA-positive cohort : FOLFIRINOX | Experimental | Drug: FolfirinoxctDNA-positive patients will be randomized to escalation treatment (5FU + irinotecan + oxaliplatin [FOLFIRINOX] for 6 months). |
| ctDNA-positive cohort : FOLFOX | Active comparator | Drug: FOLFOX regimenctDNA-positive patients will be randomized to standard treatment (FOLFOX for 6 months). |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent
- Age ≥18 years and <80 years (for patients aged >70 years: G8 geriatric questionnaire score>14)
- Histologically confirmed stage III pMMR/MSS colon and high rectum adenocarcinoma (T, N1 or N2, M0) excluding medium and low rectal cancers (≥12 cm from the anal verge by endoscopy and/or above the peritoneal reflection at surgery are still eligible), without gross or microscopic evidence of residual disease after surgery with curative intent.
- No metastatic disease on CT-Scan and/or liver MRI done within 2 months before inclusion
- Inclusion planned between 10 days to 6 weeks after surgery
Key exclusion criteria (13 listed)
- Peripheral neuropathy grade ≥1
- Patients who have received neo-adjuvant treatment.
- Comorbidity influencing the 3-year patients' survival including clinically relevant cardiovascular disease, such as Ischemic myocardial infarction in the last year and/or unstable ischemic cardiopathy
- Contra-indication to chemotherapy (inadequate bone marrow, hepatic, renal functions, hypersensitivity to one of the treatments or any of the excipients)
- Patient must not have received bone marrow transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CapecitabineDe-escalation treatment (capecitabine [CAPE] for 6 months). Or Standard treatment (CAPOX for 3 months) | Drug | ctDNA-negative cohort : Capecitabine + oxaliplatin, ctDNA-negative cohort : Capecitabine alone |
| OxaliplatinStandard treatment (CAPOX for 3 months) | Drug | ctDNA-negative cohort : Capecitabine + oxaliplatin |
| FolfirinoxEscalation treatment (5FU + irinotecan + oxaliplatin [FOLFIRINOX] for 6 months) | Drug | ctDNA-positive cohort : FOLFIRINOX |
| FOLFOX regimenStandard treatment (FOLFOX for 6 months) | Drug | ctDNA-positive cohort : FOLFOX |
Primary outcome
Non-inferiority of 6-month CAPE vs 3-month CAPOX ACT in terms of 3-year Disease Free Survival ctDNA-negative cohort
Time frame: DFS will be defined as time from date of randomization until the date of first documented recurrence local or metastatic, date of second colorectal cancer, or date of death from any cause wichever came first, assessed up to 42 months.
ctDNA-negative cohort: The primary objective is to evaluate the non-inferiority of 6-month capecitabine alone (CAPE; de-escalation strategy) compared to 3-month capecitabine + oxaliplatin (CAPOX; standard therapy) in terms of 3-year disease-free survival (DFS) as adjuvant chemotherapy (ACT) protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-negative.
Superiority of 6-month FOLFIRINOX vs 6-month FOLFOX ACT in terms of 3-year Disease Free Survival ctDNA-positive cohort
Time frame: DFS will be defined as time from date of randomization until the date of first documented recurrence local or metastatic, date of second colorectal cancer, or date of death from any cause, wichever came first, assessed up to 42 months.
ctDNA-positive cohort: The primary objective is to evaluate the superiority of 6-month FOLFIRINOX (escalation strategy) compared to 6-month FOLFOX (standard therapy) in terms of 3-year DFS as an ACT protocol in stage III pMMR/MSS CRC patients with post-operative ctDNA-positive.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Capecitabine, Oxaliplatin and Folfirinox in people with Colorectal Cancer, run by UNICANCER at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 22 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Sweden, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-inferiority of 6-month CAPE vs 3-month CAPOX ACT in terms of 3-year Disease Free Survival ctDNA-negative cohort (time frame: DFS will be defined as time from date of randomization until the date of first documented recurrence local or metastatic, date of second colorectal cancer, or date of death from any cause wichever came first, assessed up to 42 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2026.