Colon Cancer (Stage II &Amp;Amp; III)Phase 2OPTICAL-3NCT06890624
mFOLFOXIRI Plus PD-1 Inhibitor vs mFOLFOX6 as Neoadjuvant Therapy for Locally Advanced Colon Cancer
A Phase 2 study testing cmFOLFOXIRI plus PD-1 inhibitor and mFOLFOX6 in people with Colon Cancer (Stage II &Amp;Amp; III), run by Sun Yat-sen University.
Trial summary
In patients with high-risk stage II and stage III colon cancer, curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become the standard treatment. However, 20 to 30% of these patients will develop distant metastasis, which ultimately results in death. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colon Cancer (Stage II &Amp;Amp; III)
- What is being tested?
- cmFOLFOXIRI plus PD-1 inhibitor and mFOLFOX6
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 1 Oct 2031
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon (≥ 12 cm from the anal verge).
- Determined preoperatively by either spiral or multidetector CT: T4 or N2.
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- CT or MRI scans (done within 30 days of registration) of the chest, abdomen and pelvis all without clear evidence of distant metastatic (M1) disease.
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- No clinically significant obstruction, perforation, or bleeding related to the primary tumor.
- No previous any systemic anticancer therapy for colon cancer disease.
- Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment
Who cannot join
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.5.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
- Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.
- Breast- feeding or pregnant women
- Lack of effective contraception.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Chinese Modified FOLFOXIRI Combined With PD-1 Inhibitor Versus mFOLFOX6 as Neoadjuvant Therapy for Locally Advanced Colon Cancer (cT4/N2): A Multicenter, Randomized, Controlled, Phase II Trial
In patients with high-risk stage II and stage III colon cancer, curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become the standard treatment. However, 20 to 30% of these patients will develop distant metastasis, which ultimately results in death. In contrast to rectal cancer, the role of preoperative therapy in colon cancer is less well established. Relatively few phase III trials of preoperative therapy have been reported, although current NCCN guidelines do recommend neoadjuvant chemotherapy with FOLFOX or CAPOX regimen as an option for bulky T4b tumors. Neoadjuvant chemotherapy is an attractive approach for several reasons. The ability to deliver systemic therapies earlier in the treatment course to eradicate micrometastatic disease is conceptually appealing. In addition, surgery can stimulate tumor proliferation through inflammation and other immune pathways. Preoperative delivery of chemotherapy may also lead to higher rates of R0 resections, and chemotherapy tolerance can be better in the neoadjuvant setting, especially in colorectal surgeries that require prolonged recovery.
In the phase III study of the FOxTROT trial, the pCR rate for 6 weeks of neoadjuvant FOLFOX chemotherapy was only 4%, and a moderate or greater tumor regression was reported in 21% of patients in the NAC group. Our team also conducted the phase III OPTICAL trial, which utilized a longer period of NAC (12 weeks) with FOLFOX or CAPOX. In this trial, the pCR rate for the neoadjuvant chemotherapy group was 7%, and the downstaging rate (ypT0-2N0) was 20%. However, for patients with locally advanced colon cancer, particularly those with T4b and bulky nodal disease, the use of oxaliplatin- and fluoropyrimidine-based doublet chemotherapy does not adequately meet the clinical need for tumor shrinkage and downstaging. There is an urgent need to explore drugs with different mechanisms of action in combination with chemotherapy to improve efficacy.
Read the detailed description
This trial is a two-arm, multicenter, open-label, prospective, randomized phase II study. Eligible patients with locally advanced (T4 or N2) colon cancer will be randomly assigned in a 1:1 ratio to receive either cmFOLFOXIRI plus a PD-1 inhibitor or mFOLFOX6 as neoadjuvant treatment.
- Conditions
- Colon Cancer (Stage II &Amp;Amp; III)
- Being tested
- cmFOLFOXIRI plus PD-1 inhibitor, mFOLFOX6
- Keywords
- colon cancer
- Medical subject headings
- Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cmFOLFOXIRI plus PD-1 inhibitorDrug
cmFOLFOXIRI: oxaliplatin 85 mg/m² , irinotecan 150 mg/m², folinic acid 400 mg/m², 5-FU 2400 mg/m² continuous 46h infusion, repeat once every 2 weeks. PD-1 inhibitor 200mg, repeat once every 2 weeks.
mFOLFOX6Drug
mFOLFOX6: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hours, repeat once every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| cmFOLFOXIRI plus PD-1 inhibitor | Experimental | cmFOLFOXIRI: oxaliplatin 85 mg/m² , irinotecan 150 mg/m², folinic acid 400 mg/m², 5-FU 2400 mg/m² continuous 46h infusion, repeat once every 2 weeks. PD-1 inhibitor 200mg, repeat once every 2 weeks. For 4 cycles before surgery. Receives: Drug: cmFOLFOXIRI plus PD-1 inhibitor |
| mFOLFOX6 | Active comparator | mFOLFOX6: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hours, repeat once every 2 weeks. For 4 cycles before surgery. Receives: Drug: mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic complete response rate
The percentage of subjects with no residual viable tumor in the resected primary tumor specimen and all sampled regional lymph nodes after radical surgery (ypT0N0).
Measured: 1 year
Secondary outcomes (4)
R0 resection rate
The proportion of patients whose tumors are completely removed without residual cancer cells under the microscope. None of the following conditions can be considered as R0 resection: non-complete resection of the tumor, positive circumferential, proximal, or distal resection margin (resection margin of >1 mm).
Measured: 1 year
Event-free survival (EFS)
The time between randomization and one of the following events: locally progressive disease leading to an unresectable tumor, local R2 resection, local recurrence after an R0/1 resection, distant metastases, a new primary colorectal cancer, or death from any cause, whichever occurred first.
Measured: 3 years
Disease-free survival (DFS)
The time from the date of surgery to the date of locoregional recurrence, distant metastases, a new primary colorectal cancer, or death from any cause, whichever occurred first.
Measured: 3 years
Overall survival (OS)
The time from randomization to death from any cause. Subjects who are still alive at the time of the analysis will be censored for OS on the latest known survival date.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2025
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colon Cancer (Stage II &Amp;Amp; III)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06890624
- Sponsor's protocol ID
- CSWOG-C06
- Other IDs
- C06
- Acronym
- OPTICAL-3
- Status last verified
- May 2026
- First submitted
- 17 Mar 2025
- Last updated
- 22 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Chinese Modified FOLFOXIRI Combined With PD-1 Inhibitor Versus mFOLFOX6 as Neoadjuvant Therapy for Locally Advanced Colon Cancer (cT4/N2): A Multicenter, Randomized, Controlled, Phase II Trial
- ClinicalTrials.gov ID
- NCT06890624
- Acronym / sponsor ID
- OPTICAL-3 / CSWOG-C06
- Conditions
- Colon Cancer (Stage II &Amp;Amp; III)
- Keywords
- colon cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Oct 2031 (estimated)
- First posted
- 24 Mar 2025 (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.
In patients with high-risk stage II and stage III colon cancer, curative surgery followed by adjuvant chemotherapy with FOLFOX or CAPOX regimens has become the standard treatment. However, 20 to 30% of these patients will develop distant metastasis, which ultimately results in death. In contrast to rectal cancer, the role of preoperative therapy in colon cancer is less well established. Relatively few phase III trials of preoperative therapy have been reported, although current NCCN guidelines do recommend neoadjuvant chemotherapy with FOLFOX or CAPOX regimen as an option for bulky T4b tumors. Neoadjuvant chemotherapy is an attractive approach for several reasons. The ability to deliver systemic therapies earlier in the treatment course to eradicate micrometastatic disease is conceptually appealing. In addition, surgery can stimulate tumor proliferation through inflammation and other immune pathways. Preoperative delivery of chemotherapy may also lead to higher rates of R0 resections, and chemotherapy tolerance can be better in the neoadjuvant setting, especially in colorectal surgeries that require prolonged recovery.
In the phase III study of the FOxTROT trial, the pCR rate for 6 weeks of neoadjuvant FOLFOX chemotherapy was only 4%, and a moderate or greater tumor regression was reported in 21% of patients in the NAC group. Our team also conducted the phase III OPTICAL trial, which utilized a longer period of NAC (12 weeks) with FOLFOX or CAPOX. In this trial, the pCR rate for the neoadjuvant chemotherapy group was 7%, and the downstaging rate (ypT0-2N0) was 20%. However, for patients with locally advanced colon cancer, particularly those with T4b and bulky nodal disease, the use of oxaliplatin- and fluoropyrimidine-based doublet chemotherapy does not adequately meet the clinical need for tumor shrinkage and downstaging. There is an urgent need to explore drugs with different mechanisms of action in combination with chemotherapy to improve efficacy.
Detailed description
This trial is a two-arm, multicenter, open-label, prospective, randomized phase II study. Eligible patients with locally advanced (T4 or N2) colon cancer will be randomly assigned in a 1:1 ratio to receive either cmFOLFOXIRI plus a PD-1 inhibitor or mFOLFOX6 as neoadjuvant treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| cmFOLFOXIRI plus PD-1 inhibitor | Experimental | Drug: cmFOLFOXIRI plus PD-1 inhibitorcmFOLFOXIRI: oxaliplatin 85 mg/m² , irinotecan 150 mg/m², folinic acid 400 mg/m², 5-FU 2400 mg/m² continuous 46h infusion, repeat once every 2 weeks. PD-1 inhibitor 200mg, repeat once every 2 weeks. For 4 cycles before surgery. |
| mFOLFOX6 | Active comparator | Drug: mFOLFOX6mFOLFOX6: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hours, repeat once every 2 weeks. For 4 cycles before surgery. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Willing and able to provide written informed consent.
- Histological or cytological documentation of adenocarcinoma of the colon (≥ 12 cm from the anal verge).
- Determined preoperatively by either spiral or multidetector CT: T4 or N2.
- Male or female subjects > 18 years < 70 of age.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (8 listed)
- Previous or concurrent cancer that is distinct in primary site or histology from colon cancer within 5 years prior to randomization.
- Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment.
- Heart failure grade III/IV (NYHA-classification).
- Unresolved toxicity higher than CTCAE v.5.0 Grade 1 attributed to any prior therapy/procedure.
- Subjects with known allergy to the study drugs or to any of its excipients.
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 |
|---|---|---|
| cmFOLFOXIRI plus PD-1 inhibitorcmFOLFOXIRI: oxaliplatin 85 mg/m² , irinotecan 150 mg/m², folinic acid 400 mg/m², 5-FU 2400 mg/m² continuous 46h infusion, repeat once every 2 weeks. PD-1 inhibitor 200mg, repeat once every 2 weeks. | Drug | cmFOLFOXIRI plus PD-1 inhibitor |
| mFOLFOX6mFOLFOX6: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 IV bolus, followed by 2400 mg/m2 continuous IV infusion over 46 hours, repeat once every 2 weeks. | Drug | mFOLFOX6 |
Primary outcome
Pathologic complete response rate
Time frame: 1 year
The percentage of subjects with no residual viable tumor in the resected primary tumor specimen and all sampled regional lymph nodes after radical surgery (ypT0N0).
4 secondary outcomes
R0 resection rate
Time frame: 1 year
Event-free survival (EFS)
Time frame: 3 years
Disease-free survival (DFS)
Time frame: 3 years
Overall survival (OS)
Time frame: 5 years
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 May 2026.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing cmFOLFOXIRI plus PD-1 inhibitor and mFOLFOX6 in people with Colon Cancer (Stage II &Amp;Amp; III), run by Sun Yat-sen University.
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 9 inclusion and 8 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: opening soon, as of the sponsor's last update on 22 May 2026. Status can change between updates, so confirm with the study contact before making plans.
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?
Contact Yanhong Deng Professor Deng, M.D. (008613925106525, dengyanh@mail.sysu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response rate (time frame: 1 year). 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 May 2026.