Clinical trial NCT06154538: Cadonilimab + FOLFOX Versus FOLFOX in the Neoadjuvant Treatment of pMMR/MSS Locally Advanced Colorectal Cancer
Official title: Comparison of Cetuximab Combined With Chemotherapy Versus Chemotherapy Alone in the Neoadjuvant Treatment of Locally Advanced pMMR/MSS Colorectal Cancer: a Randomized, Open-label, Single-center Phase II Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Locally Advanced Colorectal Carcinoma
Lead sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Sponsor class: OTHER
First posted: 2023-12-04
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to compare the efficacy and safety of the combination of Cadonilimab and FOLFOX regimen compared to FOLFOX regimen alone in the neoadjuvant chemotherapy of pMMR/MSS locally advanced colorectal cancer. The main question aims to answer are:

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

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

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

Detailed description: A prospective, randomized, open, single-center clinical study evaluating the efficacy (pathological response, survival outcomes) and safety of the combination of Cadonilimab and FOLFOX regimen compared to FOLFOX regimen in the treatment of locally advanced colorectal cancer with proficient mismatch-repair (pMMR) or microsatellite stable (MSS) protein expression.

Eligibility criteria: 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, with mismatch repair protein expression result of pMMR, or microsatellite instability testing result of MSS;
* 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 adenocarcinoma but mismatch repair protein expression result is dMMR, or microsatellite instability testing result is MSI-H; or 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.

Primary outcomes:
measure: pCR rate
timeFrame: at time of surgery
Secondary outcomes:
measure: R0 resection rate
timeFrame: at time of surgical assessment (after 3 cycles), up to 12 months
measure: DFS
timeFrame: up to 3 years after intervention
measure: 3 years DFS rate
timeFrame: 3 years
measure: OS
timeFrame: at 1,2,3 years at follow-up time
Other outcomes:
measure: adverse event adverse event rate
timeFrame: 90 days
measure: treatment-related adverse event
timeFrame: 90 days
measure: serious adverse event
timeFrame: 90 days
Locations:
city: Beijing
country: China
facility: Cancer Hospital/ National Cancer Center, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: vice director of colorectal surgery dept.
name: Qian Liu
role: PRINCIPAL_INVESTIGATOR
affiliation: vice director of medical oncology dept.
name: Jing Huang
role: STUDY_DIRECTOR
References: