Immune Checkpoint Inhibitors + Chemotherapy Versus Chemotherapy in the Neoadjuvant Treatment of Locally Advanced Colorectal Cancer

Comparison of Immune Checkpint Inhibitors Combined With Chemotherapy Versus Chemotherapy Alone in the Neoadjuvant Treatment of Locally Advanced Colorectal Cancer: a Randomized, Open-label, Single-center Phase II Clinical Study

The goal of this clinical trial is to compare the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and FOLFOX regimen compared to FOLFOX regimen alone in the neoadjuvant chemotherapy of locally advanced colorectal cancer. The main question aims to answer are:

Question 1: Compare the pathological complete response rate between the combination of ICIs and FOLFOX regimen and the FOLFOX alone.

Question 2: Compare the survival outcomes and safety between the combination of ICIs and FOLFOX regimen and the FOLFOX alone.

Two groups of participants will receive different new adjuvant chemotherapy regimens, and their efficacy will be compared.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Colorectal Carcinoma
• Intervention / Treatment: Drug: FOLFOX regimen; Drug: Immune checkpoint inhibitor

Detailed Description

A prospective, randomized, open, multi-center clinical study evaluating the efficacy (pathological response, survival outcomes) and safety of the combination of ICIs and FOLFOX regimen compared to FOLFOX regimen in the treatment of locally advanced colorectal cancer.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qian Liu; Phone Number: +8618610506948; Email: fcwpumch@163.com
• Study Contact Backup: Name: Xiyue Hu; Phone Number: +8618610506948; Email: hxy1101bjmu@163.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100038
      • Recruiting
      • Cancer Hospital/ National Cancer Center, Chinese Academy of Medical Sciences
      • Contact: Xiyue Hu; Phone Number: +8618610506948; Email: hxy1101bjmu@163.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Fan Chen
      • Principal Investigator: Fan Chen
  • Shandong
    • Jinan, Shandong, China, 250000
      • Recruiting
      • QiLU Hospital of ShanDong University
      • Contact: Shuohui Dong
      • Principal Investigator: Shuohui Dong, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 to 75, no gender restrictions;
• Histologically or cytologically confirmed colorectal adenocarcinoma;
• Clinically diagnosed as stage II/III colorectal cancer based on CT and/or MRI (according to the 8th edition of AJCC staging);
• Sufficient tumor tissue specimens for mismatch repair protein expression or microsatellite instability testing;
• No prior systemic drug therapy and/or radiotherapy for colorectal adenocarcinoma;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Normal major organ function, no severe blood, heart, lung, liver, kidney dysfunction, or immune deficiency diseases (see protocol for details);
• Voluntary participation in this study and signed informed consent form;
• Expected good compliance to complete the study treatment, follow-up for efficacy and adverse reactions according to the protocol requirements.

Exclusion Criteria:

• Pathology is other malignant tumors besides adenocarcinoma, such as squamous cell carcinoma, gastrointestinal stromal tumor, melanoma, etc.;
• Within 5 years prior to the first use of investigational drug, diagnosed with other malignant tumors, excluding effectively treated basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ cervical cancer and/or breast cancer effectively removed;
• Any distant metastatic colorectal adenocarcinoma (according to AJCC 8th edition staging, determined as M1), including but not limited to distant lymph node metastasis, liver metastasis, lung metastasis, intraperitoneal dissemination, or malignant peritoneal effusion;
• Various severe underlying diseases and autoimmune diseases (see protocol for details);
• Unable to control recurrent bleeding or subjects who received blood transfusion within 2 weeks prior to the first use of investigational drug;
• Any other circumstances where the investigator believes it may increase the risk associated with participating in the study, the administration of the investigational drug, or affect the subject's ability to receive the investigational drug and the reliability of the study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: FOLFOX group; Patients in this group will undergo FOLFOX chemotherapy regimen, specifically: Oxaliplatin 85 mg/m2 dissolved in 500 ml of 5% glucose solution, intravenous drip, on Day 1, in combination with calcium folinate (400mg/m2), intravenous infusion, on Day 1, and 5-FU (400mg/m2), intravenous infusion, on Day 1, followed by continuous intravenous infusion of 1200mg/(m2·d) for 2 days (total dose of 2400mg/m2, infusion for 46-48 hours), once every 2 weeks. After 3 cycles of preoperative treatment, imaging evaluation will be performed. If the disease is resectable, surgery will be performed. If R0 resection is achieved, the preoperative treatment regimen will be continued after surgery, for a maximum of 9 cycles.	Drug: FOLFOX regimen; FOLFOX chemotherapy
Experimental: ICIs + FOLFOX group; Patients in this group will receive ICIs combined with FOLFOX regimen, specifically: ICIs, intravenous infusion, D1; Oxaliplatin (85mg/m2), intravenous infusion, D1; Calcium folinate (400mg/m2), intravenous infusion, D1; 5-FU (400mg/m2), intravenous infusion, D1, then continuous intravenous infusion of 1200mg/(m2·d)×2d (total amount of 2400mg/m2, infusion for 46-48h) every two weeks. Imaging evaluation will be performed after 3 cycles of preoperative treatment. If the disease is resectable, surgery will be performed. If R0 resection is achieved, the preoperative regimen will continue for up to 9 cycles.	Drug: FOLFOX regimen; FOLFOX chemotherapy; Drug: Immune checkpoint inhibitor; PD-1 antibody; Other Names: 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR rate	pathological complete response rate	at time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 resection rate	at time of surgical assessment (after 3 cycles), up to 12 months
DFS	disease-free survival	up to 3 years after intervention
3 years DFS rate	3 years DFS rate	3 years
OS	overall survival	at 1,2,3 years at follow-up time

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event adverse event rate	adverse event	90 days
treatment-related adverse event	treatment-related adverse event	90 days
serious adverse event	serious adverse event	90 days

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Principal Investigator: Qian Liu, vice director of colorectal surgery dept.; Study Director: Jing Huang, vice director of medical oncology dept.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: November 12, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): December 4, 2023

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 22, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors; Folfox protocol
• Other Study ID Numbers: CancerIHCAMS-NCTplusAK104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No