Chemo plus anti-PD-1 therapy and sitagliptin before surgery for locally advanced pMMR colorectal cancer
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 trial tests whether adding sitagliptin and an anti‑PD‑1 antibody to standard pre‑surgery chemotherapy can increase tumor shrinkage in adults with locally advanced pMMR colorectal cancer.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 138 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Second Affiliated Hospital, School of Medicine, Zhejiang University Academic / other |
| Drugs / interventions | chemotherapy, immunotherapy |
| Locations | 1 site (Hangzhou, Zhejiang) |
| Trial ID | NCT07365592 on ClinicalTrials.gov |
What this trial studies
This is a combined phase Ib/II trial testing the safety and activity of sitagliptin added to XELOX chemotherapy and an anti‑PD‑1 monoclonal antibody as neoadjuvant treatment for proficient mismatch repair (pMMR) colorectal cancer. The phase Ib portion is a single‑center 3+3 dose‑escalation study to determine the recommended phase II dose of sitagliptin and to characterize safety and immune changes in the tumor microenvironment. The phase II portion is a prospective, randomized controlled superiority trial conducted across centers to compare the combination regimen with the current standard approach for locally advanced disease. Primary aims include safety, degree of tumor regression prior to surgery, and exploratory immune biomarkers associated with response.
Who should consider this trial
Good fit: Ideal candidates are adults 18–75 years old with pathologically confirmed colorectal adenocarcinoma staged T3‑4aNany or TanyN1‑2 without distant metastasis, confirmed pMMR by immunohistochemistry, and who are fit for chemotherapy with life expectancy of at least one year.
Not a fit: Patients with distant metastasis, multifocal colorectal cancer, major uncontrolled organ disease, inability to receive chemotherapy, or those who refuse participation are unlikely to benefit from this neoadjuvant combination.
Why it matters
Potential benefit: If successful, the combination could increase the degree of tumor regression before surgery and potentially reduce recurrence for patients with locally advanced pMMR colorectal cancer.
How similar studies have performed: Single‑agent PD‑1 therapies have limited activity in pMMR CRC, combination chemo‑immunotherapy approaches have shown only modest and variable signals in this population, and adding a DPP‑4 inhibitor like sitagliptin to this regimen is a relatively novel strategy with limited prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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
Where this trial is running
Hangzhou, Zhejiang
- Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
Study contacts
- Study coordinator: Jun Li, MD
- Email: 2307016@zju.edu.cn
- Phone: +86 13777878061
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.