Colorectal Neoplasms MalignantPhase 2NCT07821333
Circulating Tumor DNA Based Decision for Adjuvant Treatment in Colon Cancer Stage II-III
A Phase 2 study testing FOLFOXIRI and CAPOX in people with Colorectal Neoplasms Malignant and Minimal Residual Disease, run by Fundación para la Investigación del Hospital Clínico de Valencia at 7 sites in Spain.
Trial summary
This trial has been designed to prove the feasibility of using liquid biopsy detection of minimal residual disease (MRD) to guide the postsurgical clinical management of early colon cancer patients. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms Malignant, Minimal Residual Disease, Circulating Tumor Cell
- What is being tested?
- FOLFOXIRI and CAPOX
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 7 sitesSpain
- Study dates
- 1 Jan 2022to 1 Jan 2027
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- CIRCULATE-SPAIN-01 trial written informed consent.
- Age ≥ 18 years and ≤ 75 years.
- Histologically confirmed diagnosis of operable stage II or stage III Colon Cancer.
- Postoperative, ctDNA positive.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Normal organ functions, as follows:
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- Absolute neutrophil count (ANC) ≥ 1500/μL.
- Platelets ≥ 100.000/μL.
- Hemoglobin ≥ 9.0 g/dL OR ≥ 5.6 mmol/L.
- Total bilirubin ≤ 1.5 x upper level of normality (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 x ULN.
- Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) ≤ 2.5 x ULN.
- Note: Synchronous primary tumours are accepted. Note: Patients with rectal cancer above the peritoneal reflection, who have not undergone postoperative chemotherapy or radiotherapy and who have risk factors, may be included in the trial.
Who cannot join
- Patients having a MicroSatellite Instability High (MSI-H) or MisMatch Repair Deficient (MMRd) tumor are excluded from the study (done according to standard clinical practice).
- History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Had an incomplete diagnostic colonoscopy and/or polyps' removal for patients in whom the remaining colon was not removed or explored. Note: Patients with intraoperative complete colonoscopy or early perioperative complete colonoscopy and/or patients with incomplete colonoscopy, but who do have a CT Colono or Intraoperative Colonoscopy, may be eligible to be recruited in the study.
- Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
- Current treatment with another investigational drug or participation in another investigational study.
- Patient unable to comply with the study protocol owing to psychological, social or geographical reasons.
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- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
- Inadequate contraception (male or female patients) if of childbearing or procreational potential.
- Current clinically unresolved cardiovascular disease.
- Acute or subacute intestinal occlusion or history of inflammatory bowel disease.
- Pre-existing neuropathy > grade 1. Known grade 3 or 4 allergic reaction to any of the components of the treatment.
- Has a known DihydroPyrimidine Dehydrogenase (DPD) deficiency.
- Has a known Gilbert Syndrome or UGT1A1 homozygous *28/*28 germline variant.
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection. Note: no testing for Hepatitis B and Hepatitis C is required.
- Has a known history of active Bacillus Tuberculosis (TB).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Spain7 sites
Hospital del Mar
Barcelona, 08003
Hospital Universitari Vall D'Hebron
Barcelona, 08035
Hospital Universitario Reina Sofía
Córdoba, 14004
Hospital Universitario de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Universitario 12 de Octubre
Madrid, 28041
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital General Universitario de Valencia
Valencia, 46014
About this study
Official title: Phase II Randomized Trial to Assess the Effect of Intensive vs Standard Adjuvant Chemotherapy in Localized Colon Cancer With Circulating Tumor DNA
This trial has been designed to prove the feasibility of using liquid biopsy detection of minimal residual disease (MRD) to guide the postsurgical clinical management of early colon cancer patients. Moreover, it is important to define if conventional (CAPOX) versus intensive (FOLFOXIRI) adjuvant chemotherapy could convert plasma ctDNA positive into a ctDNA negative status.
Read the detailed description
The detection of circulating tumor DNA immediately after surgery with curative-intent identifies minimal residual disease and has been demonstrated as a surrogate of disease-free survival. This finding could guide adjuvant postoperative treatment in early colon cancer patients.
The efficacy and safety of FOLFOXIRI were previously tested in metastatic colorectal cancer patients. The Investigators hypothesize that an intensive adjuvant chemotherapy with FOLFOXIRI regimen could convert patients with detectable ctDNA into ctDNA negative indicating appropriate control of minimal residual disease. Moreover, FOLFOXIRI could have a higher conversion rate than conventional CAPOX therapy.
The current trial proposes a two-step approach. In the first part, a maximum of 40 patients with positive plasma ctDNA will be receiving an intensive adjuvant treatment with FOLFOXIRI, which is considered at the moment standard of care for metastatic patients. This part will be taken as a go/no go decision. The aim is to get at least 14 patients with ctDNA negative after such adjuvant treatment. If these figures are not met, the trial will be stopped due to futility, recognizing that such adjuvant treatment cannot control MRD. On the other hand, if these numbers are reached, a second part is designed as an exploratory phase II study to further randomize 124 patients with ctDNA positive into CAPOX versus FOLFOXIRI for six months, assessing again ctDNA conversion into a negative status. The aim of this part is to estimate differences in converting plasma ctDNA into negative among the conventional versus intensive adjuvant treatment.
- Being tested
- FOLFOXIRI, CAPOX
- Medical subject headings
- Colonic Neoplasms, Neoplasm, Residual, Neoplastic Cells, Circulating
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOLFOXIRIDrug
Also called intensive adjuvant chemotherapy
Patients will receive 12 cycles each 14 days
CAPOXDrug
Also called standard adjuvant chemotherapy
Patients will receive 8 cycles each 21 days
| Study group | Role | What they receive |
|---|---|---|
| FOLFOXIRI | Experimental | FOLFOXIRI intensive adjuvant chemotherapy Receives: Drug: FOLFOXIRI |
| CAPOX | Active comparator | CAPOX standard adjuvant chemotherapy Receives: Drug: CAPOX |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with ctDNA clearance following FOLFOXIRI treatment
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following intensive adjuvant treatment with FOLFOXIRI.
Measured: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIa).
Difference in ctDNA clearance rate between FOLFOXIRI and CAPOX(FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following adjuvant chemotherapy, compared between the intensive treatment group (FOLFOXIRI) and the standard-of-care group (CAPOX).
Measured: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIb).
Secondary outcomes (5)
Disease-free survival in patients with positive ctDNA
Disease-free survival in patients with positive circulating tumor DNA (ctDNA), compared between the FOLFOXIRI and CAPOX treatment groups.
Measured: At 24 months after the end of treatment (phase IIb).
Disease-free survival according to ctDNA clearance status
Disease-free survival according to ctDNA clearance status (patients with positive ctDNA who become ctDNA-negative versus patients who remain ctDNA-positive), evaluated in each treatment arm.
Measured: At 12 months after the end of treatment (phase IIb).
Treatment-related toxicity of FOLFOXIRI compared with CAPOX
Incidence and severity of treatment-related adverse events during adjuvant chemotherapy, compared between patients treated with FOLFOXIRI and those treated with CAPOX.
Measured: During the treatment period and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), comparing scores between the FOLFOXIRI and CAPOX treatment groups.
All scales and single-item measures are transformed to scores ranging from 0 to 100. Higher scores on functional scales represent a higher/healthier level of functioning, and a higher score on the global health status/quality of life scale represents better quality of life. Higher scores on symptom scales or symptom items represent a higher level of symptoms or problems and therefore a worse outcome.
Measured: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29)
Colorectal cancer-specific quality of life, functioning, and symptoms will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29), comparing scores between the FOLFOXIRI and CAPOX treatment groups.
All scales and single-item measures are transformed to scores ranging from 0 to 100. Higher scores on functional scales represent a higher/healthier level of functioning, whereas higher scores on symptom scales or symptom items represent a higher level of symptoms or problems and therefore a worse outcome.
Measured: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2026
- Study start1 Jan 2022
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Neoplasms MalignantStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This is a single to double arm transition study in which patients are firstly enrolled into a single arm (Phase IIa) study expandable to a randomized double arm (Phase IIb). In the first stage (Phase IIa) the success of the experimental treatment (FOLFOXIRI) is compared to a fixed value. If the pre-fixed result is achieved, the trial will be expanded to a phase IIb in which patients will be enrolled to randomly receive experimental treatment (FOLFOXIRI) or control (CAPOX).
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de Valencia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrés Cervantes Ruipérez, MD, Principal investigator, Hospital Clínico Universitario de Valencia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07821333
- Sponsor's protocol ID
- CIRCULATE-SPAIN-01
- Status last verified
- Sep 2026
- First submitted
- 23 Jul 2021
- Last updated
- 15 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Trial to Assess the Effect of Intensive vs Standard Adjuvant Chemotherapy in Localized Colon Cancer With Circulating Tumor DNA
- ClinicalTrials.gov ID
- NCT07821333
- Acronym / sponsor ID
- CIRCULATE-SPAIN-01
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Fundación para la Investigación del Hospital Clínico de ValenciaUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jan 2027 (estimated)
- First posted
- 15 Sep 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.
This trial has been designed to prove the feasibility of using liquid biopsy detection of minimal residual disease (MRD) to guide the postsurgical clinical management of early colon cancer patients. Moreover, it is important to define if conventional (CAPOX) versus intensive (FOLFOXIRI) adjuvant chemotherapy could convert plasma ctDNA positive into a ctDNA negative status.
Detailed description
The detection of circulating tumor DNA immediately after surgery with curative-intent identifies minimal residual disease and has been demonstrated as a surrogate of disease-free survival. This finding could guide adjuvant postoperative treatment in early colon cancer patients.
The efficacy and safety of FOLFOXIRI were previously tested in metastatic colorectal cancer patients. The Investigators hypothesize that an intensive adjuvant chemotherapy with FOLFOXIRI regimen could convert patients with detectable ctDNA into ctDNA negative indicating appropriate control of minimal residual disease. Moreover, FOLFOXIRI could have a higher conversion rate than conventional CAPOX therapy.
The current trial proposes a two-step approach. In the first part, a maximum of 40 patients with positive plasma ctDNA will be receiving an intensive adjuvant treatment with FOLFOXIRI, which is considered at the moment standard of care for metastatic patients. This part will be taken as a go/no go decision. The aim is to get at least 14 patients with ctDNA negative after such adjuvant treatment. If these figures are not met, the trial will be stopped due to futility, recognizing that such adjuvant treatment cannot control MRD. On the other hand, if these numbers are reached, a second part is designed as an exploratory phase II study to further randomize 124 patients with ctDNA positive into CAPOX versus FOLFOXIRI for six months, assessing again ctDNA conversion into a negative status. The aim of this part is to estimate differences in converting plasma ctDNA into negative among the conventional versus intensive adjuvant treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a single to double arm transition study in which patients are firstly enrolled into a single arm (Phase IIa) study expandable to a randomized double arm (Phase IIb). In the first stage (Phase IIa) the success of the experimental treatment (FOLFOXIRI) is compared to a fixed value. If the pre-fixed result is achieved, the trial will be expanded to a phase IIb in which patients will be enrolled to randomly receive experimental treatment (FOLFOXIRI) or control (CAPOX).
| Arm | Type | Receives |
|---|---|---|
| FOLFOXIRI | Experimental | Drug: FOLFOXIRIFOLFOXIRI intensive adjuvant chemotherapy |
| CAPOX | Active comparator | Drug: CAPOXCAPOX standard adjuvant chemotherapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- CIRCULATE-SPAIN-01 trial written informed consent.
- Age ≥ 18 years and ≤ 75 years.
- Histologically confirmed diagnosis of operable stage II or stage III Colon Cancer.
- Postoperative, ctDNA positive.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Key exclusion criteria (16 listed)
- Patients having a MicroSatellite Instability High (MSI-H) or MisMatch Repair Deficient (MMRd) tumor are excluded from the study (done according to standard clinical practice).
- History of another neoplastic disease, unless in remission for ≥ 5 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- Had an incomplete diagnostic colonoscopy and/or polyps' removal for patients in whom the remaining colon was not removed or explored. Note: Patients with intraoperative complete colonoscopy or early perioperative complete colonoscopy and/or patients with incomplete colonoscopy, but who do have a CT Colono or Intraoperative Colonoscopy, may be eligible to be recruited in the study.
- Macroscopic or microscopic evidence of residual tumor (R1 or R2 resections). Patients should never have had any evidence of metastatic disease (including presence of tumor cells in the peritoneal lavage).
- Current treatment with another investigational drug or participation in another investigational study.
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 |
|---|---|---|
| FOLFOXIRIAlso: intensive adjuvant chemotherapyPatients will receive 12 cycles each 14 days | Drug | FOLFOXIRI |
| CAPOXAlso: standard adjuvant chemotherapyPatients will receive 8 cycles each 21 days | Drug | CAPOX |
Primary outcome
Proportion of patients with ctDNA clearance following FOLFOXIRI treatment
Time frame: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIa).
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following intensive adjuvant treatment with FOLFOXIRI.
Difference in ctDNA clearance rate between FOLFOXIRI and CAPOX(FOLFOXIRI) versus conventional adjuvant therapy (CAPOX).
Time frame: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIb).
Proportion of patients with detectable circulating tumor DNA (ctDNA) prior to treatment who become ctDNA-negative following adjuvant chemotherapy, compared between the intensive treatment group (FOLFOXIRI) and the standard-of-care group (CAPOX).
5 secondary outcomes
Disease-free survival in patients with positive ctDNA
Time frame: At 24 months after the end of treatment (phase IIb).
Disease-free survival according to ctDNA clearance status
Time frame: At 12 months after the end of treatment (phase IIb).
Treatment-related toxicity of FOLFOXIRI compared with CAPOX
Time frame: During the treatment period and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time frame: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
Quality of life assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal 29 (EORTC QLQ-CR29)
Time frame: At baseline, 3 months after treatment initiation, and immediately after adjuvant chemotherapy completion (phase IIb).
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 15 Sep 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.
Andrés Cervantes Ruipérez, MD principal investigator
Hospital Clínico Universitario de Valencia
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FOLFOXIRI and CAPOX in people with Colorectal Neoplasms Malignant and Minimal Residual Disease, run by Fundación para la Investigación del Hospital Clínico de Valencia at 7 sites in Spain.
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 12 inclusion and 16 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 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Proportion of patients with ctDNA clearance following FOLFOXIRI treatment (time frame: Prior to treatment initiation, immediately after adjuvant chemotherapy completion, and every 4 months for 2 years (phase IIa).). 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 15 Sep 2026.