Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer

Trial Title: Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer

NCT ID: NCT05914389

Condition: Colon Neoplasm

Conditions: Official terms:
Colonic Neoplasms
Capecitabine
Oxaliplatin
Antibodies
Antibodies, Monoclonal

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Oxaliplatin
Description: Oxaliplatin 130mg/m2 for inducing chemotherapy on Day 1 every 3 weeks and repeat for 4 cycles. The dose reduction protocol for oxaliplatin-induced toxicity was implemented according to the report in BJC (2018) 118:1322-1328.
Arm group label: Enhancement regimen of combined Anti-PD-L1 monoclonal antibody
Arm group label: Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody
Arm group label: Standard chemotherapy control cohort

Intervention type: Drug
Intervention name: Capecitabine
Description: Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy from Day 1 to Day 14 every 3 weeks and repeat for 4 cycles. The dose reduction protocol for capecitabine-induced toxicity was implemented according to the report in BJC (2018) 118:1322-1328.
Arm group label: Enhancement regimen of combined Anti-PD-L1 monoclonal antibody
Arm group label: Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody
Arm group label: Standard chemotherapy control cohort

Intervention type: Drug
Intervention name: Anti-PD-L1 Monoclonal Antibody
Description: The incidence of adverse events with Anti-PD-L1 Monoclonal Antibodies is relatively low. Based on phase I clinical trial data of Envafolimab, a dose reduction design was conducted to minimize the incidence of adverse events while ensuring therapeutic efficacy. In the two cohorts of the efficacy-enhancing design, a reduced dose of 100mg/0.5ml IH QW will be used for 6 weeks. The PD-L1 monoclonal antibody (Envafolimab) dose adjustment was implemented according to the prescribing information.
Arm group label: Enhancement regimen of combined Anti-PD-L1 monoclonal antibody
Arm group label: Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody

Other name: Envafolimab

Intervention type: Drug
Intervention name: Clostridium butyricum
Description: Clostridium butyricum is treated with Miyarisan 588 powder, 160mg/day (4 packets/day) taken orally for a total of 6 weeks.There have been no reports of adverse reactions for Lactobacillus. There is no predetermined reduction plan.
Arm group label: Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody

Intervention type: Procedure
Intervention name: Colectomy
Description: The specific surgical approach, whether it be laparoscopic or open surgery, is determined by the surgeon. The tumor blood supply is ligated and cut at the root of the mesentery, and the margin of resection should be no less than 10cm. Complete resection of the mesocolon (CME) is performed in conjunction.
Arm group label: Enhancement regimen of combined Anti-PD-L1 monoclonal antibody
Arm group label: Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody
Arm group label: Standard chemotherapy control cohort

Summary: This study aims to elucidate the regression effects of neoadjuvant chemotherapy combined with immunotherapy and adjuvant therapy in locally advanced MSS colon cancer.

Detailed description: The standard treatment for locally advanced colon cancer is surgery followed by adjuvant chemotherapy containing oxaliplatin. The MOSAIC and 16968 studies have shown that approximately 30% of patients experience recurrence and metastasis within 6-7 years after surgery. Neoadjuvant chemotherapy may improve the prognosis of patients with malignant tumors. The significant tumor shrinkage after neoadjuvant therapy indicates a greater likelihood of long-term survival for patients. The OPTICAL and FoxTROT studies have shown that approximately 35% of patients are resistant to oxaliplatin-containing neoadjuvant chemotherapy, with a pCR rate of less than 10% and uncertain survival improvement. In addition, immunotherapy has poor efficacy for microsatellite stable (MSS) patients. Therefore, it is necessary to explore new and effective neoadjuvant treatment modalities for tumor regression. The study will screen for individuals who are sensitive to oxaliplatin-containing regimens through induction chemotherapy. Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies for neoadjuvant therapy. In the context of cancer, the role of the intestinal microbiome in mediating immune activation induced by chemotherapy drugs has been demonstrated. Clostridium butyricum will be introduced as an adjuvant to explore the possibility of further increasing the significant response rate of neoadjuvant therapy. The study will first conduct 2 cycles of Capox induction chemotherapy to screen for patients sensitive to chemotherapy. Patients will be randomized into three cohorts: one chemotherapy standard control cohort (continuing Capox chemotherapy for 2 cycles) and two enhancement design cohorts (Capox chemotherapy + Anti-PD-L1 monoclonal antibody for 2 cycles/Capox chemotherapy + Anti-PD-L1 monoclonal antibody + Clostridium butyricum for 2 cycles), followed by CME surgery. The study's primary endpoint is the proportion of Tumor regression grade(TRG)0/1 in the pathological specimens of surgically resected tumors.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Age ≥18 years old and ≤75 years old. - Pathologically diagnosed MSS or pMMR-type colon adenocarcinoma. - The lower edge of the tumor is more than 12cm from the anus as measured by colonoscopy and the lower edge of the tumor cannot be directly palpated during rectal examination. - Enhanced CT stage T3/4 or T1-4N+ without multiple primary tumors or distant metastasis. - Life expectancy is expected to be more than 1 year. - First diagnosis, no previous anti-tumor treatment received, and no chemotherapy contraindications. - Informed consent, able to understand the study protocol and willing to participate in the study, and will provide written informed consent. Exclusion Criteria: - Refused to participate in this study. - Multifocal colorectal cancer. - History of malignant tumors, except for basal cell carcinoma, papillary thyroid carcinoma, and various in situ cancers. - Cannot tolerate chemotherapy, such as but not limited to bone marrow suppression. - Acute exacerbation of important organ diseases (such as but not limited to COPD, coronary heart disease, and renal insufficiency) and/or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia, and myocarditis), ASA score > 3 points. - Mental disorders, illiteracy, or language communication barriers that prevent the understanding of the study protocol. - Tumor obstruction or high risk of obstruction, bleeding, and/or perforation. - Peripheral sensory neuropathy, unable to receive oxaliplatin-based chemotherapy. - Pregnancy or lactation. - Unable to undergo enhanced CT examination or having comorbidities requiring the use of glucocorticoid therapy. - Continuous use of glucocorticoids for more than 3 days within 1 month prior to signing the informed consent form. - CT or MRI in the mid-sagittal plane shows that the lower border of the tumor is below the line connecting the sacrococcygeal promontory and the upper border of the pubic symphysis. - Other situations in which the researcher deems unsuitable for this study.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Second Affiliated Hospital of Zhejiang University School of Medicine

Address:
City: Hangzhou
Zip: 310000
Country: China

Status: Recruiting

Contact:
Last name: Yurong Jiao

Phone: +86 13732206364
Email: jiaoyurong1990@163.com

Start date: August 2023

Completion date: August 2030

Lead sponsor:
Agency: Second Affiliated Hospital, School of Medicine, Zhejiang University
Agency class: Other

Source: Second Affiliated Hospital, School of Medicine, Zhejiang University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05914389