Neoadjuvant Chemotherapy, Anti-PD-1 Antibody and Sitagliptin for Locally Advanced pMMR CRC

NCT07365592 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: SAHZU Jun LI
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (3)

• Adverse events (AEs)

  for Ib study

  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

  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

  1 day of postoperative pathological examination.

Secondary Outcomes (11)

• Surgical Complication

  within 30 days since operation

• Proportion of patients achieving tumor regression grade 3 (TRG 3)

  1 day of postoperative pathological examination.

• Adverse events (AEs)

  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

  1 day of postoperative pathological examination.

• Proportion of patients achieving pathological Complete Response

  1 day of postoperative pathological examination.

Other Outcomes (4)

• DPP4 activity in peripheral blood and tumor tissues

  From date of first chemotherapy until the date of patients were discharged from hospital after receiving radical surgery, up to 20 weeks

• The changes in the immunoprofile of the tumor tissue sample among TRG0/1 and TRG2/3 patients

  3 months after surgery

• 2-year overall survival

  2-year after surgery

Study Arms (2)

XELOX+sitagliptin+anti-PD-1

EXPERIMENTAL

XELOX (oxaliplatin + capecitabine), sitagliptin and PD-1 monoclonal antibody

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Anti-PD-1 monoclonal antibody; Drug: Sitagliptin (DPP4 inhibitor)

XELOX

ACTIVE COMPARATOR

XELOX (oxaliplatin + capecitabine)

Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Oxaliplatin DRUG

Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.

XELOX; XELOX+sitagliptin+anti-PD-1

Capecitabine DRUG

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.

XELOX; XELOX+sitagliptin+anti-PD-1

Anti-PD-1 monoclonal antibody DRUG

Anti-PD1 antibody 200mg/m2 in Day 1 after oxaliplatin Chemotherapy. Repeat every 3 weeks for 2 cycles.

XELOX+sitagliptin+anti-PD-1

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.

XELOX+sitagliptin+anti-PD-1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Capecitabine; spartalizumab; Sitagliptin Phosphate; Dipeptidyl-Peptidase IV Inhibitors

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Triazoles; Azoles; Pyrazines; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Hypoglycemic Agents; Physiological Effects of Drugs

Central Study Contacts

Jun Li, MD

CONTACT

+86 13777878061; 2307016@zju.edu.cn

Xinyi Zhou, MD

CONTACT

+86 18768115468; 3100102575@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief

Model Details: 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.

Study Record Dates

• First Submitted: December 8, 2025
• First Posted: January 26, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 26, 2026

Record last verified: 2025-12

Locations

CN (1)