Colorectal CancerPhase 1/2Neo-CDNCT07365592
Neoadjuvant Chemotherapy, Anti-PD-1 Antibody and Sitagliptin for Locally Advanced pMMR CRC
A Phase 1/2 study testing Oxaliplatin, Capecitabine and Anti-PD-1 monoclonal antibody in people with Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
This is an open-label, multicenter, phase Ib/II combined trial of sitagliptin, XELOX chemotherapy regimen, and PD-1 monoclonal antibody in the treatment of proficient mismatch repair locally advanced colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Oxaliplatin, Capecitabine and Anti-PD-1 monoclonal antibody
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 138 participants
- Where
- 1 siteChina
- Study dates
- 9 Apr 2026to 31 Dec 2029
- Phase
- Phase 1/2
- 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
- Pathologically diagnosed colorectal adenocarcinoma
- Age ≥18 years old and ≤75 years old
- MRI/CT stage T3-4aNany and TanyN1-2, without distant metastasis
- Life expectancy of 1 year The above
- Informed consent, no contraindications to chemotherapy exist
- pMMR diagnosed by IHC
Who cannot join
- Refused to participate in this study
- Multifocal colorectal cancer
- Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
- Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
- Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.),
- ASA score> 3
Show all 15Show fewer
- Mental disorder or illiteracy or language and communication barriers cannot understand the research plan
- Colorectal tumor has obstruction or high risk of obstruction and or there is bleeding and/or perforation
- Peripheral sensory nerve disorder, unable to receive oxaliplatin chemotherapy
- Lateral pelvic lymph node metastasis (mainly supplied by internal iliac artery)
- Pregnancy or breastfeeding
- Unable to accept MRI examination
- Consecutive use of glucocorticoids for more than 3 days within 1 month before signing the consent form
- Diabetes or impaired glucose tolerance who may require drug intervention
- Other scenarios deemed inappropriate by the investigators
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Xinyi Zhou, MD, +86 18768115468, 3100102575@zju.edu.cn
About this study
Official title: A Phase Ib/II Study of Neoadjuvant Chemotherapy Combined With Anti-PD-1 Antibody and DPP4 Inhibitor Sitagliptin for Locally Advanced pMMR Colorectal Cancer
This is an open-label, multicenter, phase Ib/II combined trial of sitagliptin, XELOX chemotherapy regimen, and PD-1 monoclonal antibody in the treatment of proficient mismatch repair locally advanced colorectal cancer.
Read the detailed description
Most colorectal cancer (CRC) cases are classified as proficient mismatch repair (pMMR) CRC. This subtype is insensitive to single-agent immunotherapy, with chemotherapy remaining the primary pharmacotherapeutic intervention. Approximately 30% of colon cancer patients develop recurrence and metastasis following initial radical resection combined with 6 months of adjuvant chemotherapy.
Neoadjuvant chemotherapy (NACT) for tumor downstaging and survival improvement represents a standard approach for locally advanced tumors. However, its application is limited to select rectal cancer populations, and its role in colon cancer remains controversial-primarily due to inadequate tumor regression observed with current regimens. Given that deep tumor regression correlates with improved survival, there is a critical need to enhance NACT efficacy.
Neo-CD adopts a combined phase Ib/II study design. Phase Ib Component
- Design: Single-center trial utilizing the traditional 3+3 dose-escalation principle.
- Objectives:
- Evaluate the safety of sitagliptin in combination with XELOX (oxaliplatin + capecitabine) and anti-PD-1 monoclonal antibody as neoadjuvant therapy for CRC.
- Determine the recommended phase II dose (RP2D) of sitagliptin.
- Explore the combination's potential for significant tumor regression and modulation of the tumor immune microenvironment.
Phase II Component
- Design: Prospective, multicenter, randomized controlled superiority trial.
- Objective: Compare the efficacy of neoadjuvant XELOX + sitagliptin + anti-PD-1 versus standard neoadjuvant XELOX in locally advanced CRC, with a focus on significant tumor regression (TRG 0/1 rate).
Study Procedures All participants will receive 2 cycles of the assigned neoadjuvant treatment, followed by radical surgery.
Primary Endpoints
- Phase Ib: Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicity (DLT).
- Phase II: Proportion of patients achieving tumor regression grade 0/1 (TRG 0/1).
- Conditions
- Colorectal Cancer
- Being tested
- Oxaliplatin, Capecitabine, Anti-PD-1 monoclonal antibody, Sitagliptin (DPP4 inhibitor)
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.
CapecitabineDrug
Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles.
Anti-PD-1 monoclonal antibodyDrug
Anti-PD1 antibody 200mg/m2 in Day 1 after oxaliplatin Chemotherapy. Repeat every 3 weeks for 2 cycles.
Sitagliptin (DPP4 inhibitor)Drug
Oral sitagliptin twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles.
In the phase Ib study, sitagliptin set at three dose groups: 100 mg/day, 200 mg/day, and 400 mg/day, and the primary endpoint of Ib study is to determine the DLT and recommended phase II dose (RP2D).
The appropriate dose level of sitagliptin will be set based on the result of Ib study.
| Study group | Role | What they receive |
|---|---|---|
| XELOX+sitagliptin+anti-PD-1 | Experimental | XELOX (oxaliplatin + capecitabine), sitagliptin and PD-1 monoclonal antibody Receives: Drug: Oxaliplatin; Drug: Capecitabine; Drug: Anti-PD-1 monoclonal antibody; Drug: Sitagliptin (DPP4 inhibitor) |
| XELOX | Active comparator | XELOX (oxaliplatin + capecitabine) Receives: Drug: Oxaliplatin; Drug: Capecitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events (AEs)
for Ib study
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Dose limiting toxicities (DLTs)
for Ib study
Measured: The DLT observation period is from the day1 of the first cycle(C1D1) to the start of the day1 of the second cycle(C2D1) dosing, each cycle is 21 days.
Proportion of patients achieving tumor regression grade 0/1 (TRG 0/1)
for II study
Measured: 1 day of postoperative pathological examination.
Secondary outcomes (11)
Surgical Complication
for II study
Measured: within 30 days since operation
Proportion of patients achieving tumor regression grade 3 (TRG 3)
for II study
Measured: 1 day of postoperative pathological examination.
Adverse events (AEs)
for II study
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Proportion of patients achieving tumor regression grade 0/1
for Ib study
Measured: 1 day of postoperative pathological examination.
Proportion of patients achieving pathological Complete Response
for Ib study
Measured: 1 day of postoperative pathological examination.
Proportion of patients achieving Major Pathologic Response
for Ib study
Measured: 1 day of postoperative pathological examination.
Area Under the Curve
for Ib study；quantitative measure of the total exposure of the body to a drug over a specific time period.
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Maximum Concentration
for Ib study; highest plasma or blood concentration of a drug achieved in the body after its administration.
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Time to Maximum Concentration
for Ib study; the length of time required for a drug to reach its maximum (peak) plasma or blood concentration in the systemic circulation after administration.
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Clearance
for Ib study; the volume of plasma or blood completely cleared of a drug per unit time by the body's eliminating organs
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Half-Life
for Ib study; the specific time required for the plasma or blood concentration of a drug in the systemic circulation to decrease by half from its peak level or steady-state level
Measured: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start9 Apr 2026
- Primary completion1 Dec 2029 (estimated)
- Study completion31 Dec 2029 (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 Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase Ib Component The study adopts the 3+3 design, with sitagliptin set at three dose groups: 100 mg/day, 200 mg/day, and 400 mg/day. Enrollment starts with 3 patients in Group 1. Dose escalates if no DLT; adds 3 patients if 1 DLT occurs. Escalation continues if ≤1/6 have DLT; stops and de-escalates if ≥2/6 have DLT. The study includes 9-18 patients, with no -1 dose group; the lower safe dose becomes MTD if needed. Phase II Component The current study presets the TRG 0/1 rate at 20% for the XELOX chemotherapy group. The study expects a TRG 0/1 rate of 30% in the investigational group, representing a 10% relative increase in significant tumor regression compared to standard therapy. This is a prospective, multicenter, two-stage randomized controlled interventional study based on a Bayesian adaptive design, with a maximum sample size of 120 patients.
- Masking
- None (open label)
- Enrolment
- 138 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jun Li, Second Affiliated Hospital, Zhejiang University, School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07365592
- Sponsor's protocol ID
- SAHZU Jun LI
- Acronym
- Neo-CD
- Status last verified
- Dec 2025
- First submitted
- 8 Dec 2025
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Study of Neoadjuvant Chemotherapy Combined With Anti-PD-1 Antibody and DPP4 Inhibitor Sitagliptin for Locally Advanced pMMR Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07365592
- Acronym / sponsor ID
- Neo-CD / SAHZU Jun LI
- Conditions
- Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 138 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 9 Apr 2026 (actual)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 26 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.
This is an open-label, multicenter, phase Ib/II combined trial of sitagliptin, XELOX chemotherapy regimen, and PD-1 monoclonal antibody in the treatment of proficient mismatch repair locally advanced colorectal cancer.
Detailed description
Most colorectal cancer (CRC) cases are classified as proficient mismatch repair (pMMR) CRC. This subtype is insensitive to single-agent immunotherapy, with chemotherapy remaining the primary pharmacotherapeutic intervention. Approximately 30% of colon cancer patients develop recurrence and metastasis following initial radical resection combined with 6 months of adjuvant chemotherapy.
Neoadjuvant chemotherapy (NACT) for tumor downstaging and survival improvement represents a standard approach for locally advanced tumors. However, its application is limited to select rectal cancer populations, and its role in colon cancer remains controversial-primarily due to inadequate tumor regression observed with current regimens. Given that deep tumor regression correlates with improved survival, there is a critical need to enhance NACT efficacy.
Neo-CD adopts a combined phase Ib/II study design. Phase Ib Component
- Design: Single-center trial utilizing the traditional 3+3 dose-escalation principle.
- Objectives:
- Evaluate the safety of sitagliptin in combination with XELOX (oxaliplatin + capecitabine) and anti-PD-1 monoclonal antibody as neoadjuvant therapy for CRC.
- Determine the recommended phase II dose (RP2D) of sitagliptin.
- Explore the combination's potential for significant tumor regression and modulation of the tumor immune microenvironment.
Phase II Component
- Design: Prospective, multicenter, randomized controlled superiority trial.
- Objective: Compare the efficacy of neoadjuvant XELOX + sitagliptin + anti-PD-1 versus standard neoadjuvant XELOX in locally advanced CRC, with a focus on significant tumor regression (TRG 0/1 rate).
Study Procedures All participants will receive 2 cycles of the assigned neoadjuvant treatment, followed by radical surgery.
Primary Endpoints
- Phase Ib: Incidence of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicity (DLT).
- Phase II: Proportion of patients achieving tumor regression grade 0/1 (TRG 0/1).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Phase Ib Component The study adopts the 3+3 design, with sitagliptin set at three dose groups: 100 mg/day, 200 mg/day, and 400 mg/day. Enrollment starts with 3 patients in Group 1. Dose escalates if no DLT; adds 3 patients if 1 DLT occurs. Escalation continues if ≤1/6 have DLT; stops and de-escalates if ≥2/6 have DLT. The study includes 9-18 patients, with no -1 dose group; the lower safe dose becomes MTD if needed. Phase II Component The current study presets the TRG 0/1 rate at 20% for the XELOX chemotherapy group. The study expects a TRG 0/1 rate of 30% in the investigational group, representing a 10% relative increase in significant tumor regression compared to standard therapy. This is a prospective, multicenter, two-stage randomized controlled interventional study based on a Bayesian adaptive design, with a maximum sample size of 120 patients.
| Arm | Type | Receives |
|---|---|---|
| XELOX+sitagliptin+anti-PD-1 | Experimental | Drug: Oxaliplatin, Drug: Capecitabine, Drug: Anti-PD-1 monoclonal antibody, Drug: Sitagliptin (DPP4 inhibitor)XELOX (oxaliplatin + capecitabine), sitagliptin and PD-1 monoclonal antibody |
| XELOX | Active comparator | Drug: Oxaliplatin, Drug: CapecitabineXELOX (oxaliplatin + capecitabine) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Pathologically diagnosed colorectal adenocarcinoma
- Age ≥18 years old and ≤75 years old
- MRI/CT stage T3-4aNany and TanyN1-2, without distant metastasis
- Life expectancy of 1 year The above
- Informed consent, no contraindications to chemotherapy exist
Key exclusion criteria (15 listed)
- Refused to participate in this study
- Multifocal colorectal cancer
- Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
- Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
- Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.),
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 |
|---|---|---|
| OxaliplatinOxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles. | Drug | XELOX, XELOX+sitagliptin+anti-PD-1 |
| CapecitabineOral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles. | Drug | XELOX, XELOX+sitagliptin+anti-PD-1 |
| Anti-PD-1 monoclonal antibodyAnti-PD1 antibody 200mg/m2 in Day 1 after oxaliplatin Chemotherapy. Repeat every 3 weeks for 2 cycles. | Drug | XELOX+sitagliptin+anti-PD-1 |
| Sitagliptin (DPP4 inhibitor)Oral sitagliptin twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 2 cycles. In the phase Ib study, sitagliptin set at three dose groups: 100 mg/day, 200 mg/day, and 400 mg/day, and the primary endpoint of Ib study is to determine the DLT and recommended phase II dose (RP2D). The appropriate dose level of sitagliptin will be set based on the result of Ib study. | Drug | XELOX+sitagliptin+anti-PD-1 |
Primary outcome
Adverse events (AEs)
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
for Ib study
Dose limiting toxicities (DLTs)
Time frame: The DLT observation period is from the day1 of the first cycle(C1D1) to the start of the day1 of the second cycle(C2D1) dosing, each cycle is 21 days.
for Ib study
Proportion of patients achieving tumor regression grade 0/1 (TRG 0/1)
Time frame: 1 day of postoperative pathological examination.
for II study
11 secondary outcomes
Surgical Complication
Time frame: within 30 days since operation
Proportion of patients achieving tumor regression grade 3 (TRG 3)
Time frame: 1 day of postoperative pathological examination.
Adverse events (AEs)
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Proportion of patients achieving tumor regression grade 0/1
Time frame: 1 day of postoperative pathological examination.
Proportion of patients achieving pathological Complete Response
Time frame: 1 day of postoperative pathological examination.
Proportion of patients achieving Major Pathologic Response
Time frame: 1 day of postoperative pathological examination.
Area Under the Curve
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Maximum Concentration
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Time to Maximum Concentration
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Clearance
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
Half-Life
Time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks
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 13 May 2026.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Oxaliplatin, Capecitabine and Anti-PD-1 monoclonal antibody in people with Colorectal Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
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 6 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Jun Li, MD (+86 13777878061, 2307016@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (AEs) (time frame: From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks). The study lists 3 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 13 May 2026.