Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer

NCT05914389 | Recruiting Phase 2

• 1 other identifier: 2023-0296
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colon Neoplasm

Outcome Measures

Primary Outcomes (1)

• TRG0/1

  The sum of tumor regression grades TRG0(disappearance of tumor) and TRG1(scattered residual tumor)(AJCC standard).

  1 day of postoperative pathological examination.

Secondary Outcomes (9)

• AE

  Adverse events (NCI CTC AE 5.0) that occurred from the first day of induction chemotherapy to one day before the surgery date(up to half a year).

• Surgical Complication

  From the day of surgery to 30 days after the operation, including intraoperative and postoperative complications.

• DFS

  From date of the patient signs the informed consent form until the date of earliest occurrence of the patient's tumor recurrence or death，whichever came first, assessed up to 36 months.

• OS

  From the date of the patient signs the informed consent form until the date of the patient's death, assessed up to 60 months.

• Concentration of FLT3L

  blood tests for FLT3LG at initial diagnosis, after induction chemotherapy, before and 3 months after surgery.

Study Arms (3)

Standard chemotherapy control cohort

EXPERIMENTAL

Patients with locally advanced colon cancer who met the inclusion criteria received two cycles of Capecitabine and Oxaliplatin （Capox） regimen chemotherapy and were evaluated by enhanced CT. Patients with more than 20% regression of maximum diameter of colon tumor in enhanced CT image will be randomly assigned to the Standard chemotherapy control cohort and continued with two more cycles of Capox chemotherapy. Then, these patients will receive curative surgery for colon cancer.

Drug: Oxaliplatin; Drug: Capecitabine; Procedure: Colectomy

Enhancement regimen of combined Anti-PD-L1 monoclonal antibody

EXPERIMENTAL

Patients with locally advanced colon cancer who met the inclusion criteria received two cycles of Capecitabine and Oxaliplatin （Capox） regimen chemotherapy and were evaluated by enhanced CT. Patients with more than 20% regression of maximum diameter of colon tumor in enhanced CT image will be randomly assigned to the Enhancement regimen of combined Anti-PD-L1 monoclonal antibody and continued with two more cycles of Capox chemotherapy along with the reduced dosage of Anti-PD-L1 monoclonal antibody. Then, these patients will receive curative surgery for colon cancer.

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Anti-PD-L1 Monoclonal Antibody; Procedure: Colectomy

Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody

EXPERIMENTAL

Patients with locally advanced colon cancer who met the inclusion criteria received two cycles of Capecitabine and Oxaliplatin （Capox） regimen chemotherapy and were evaluated by enhanced CT. Patients with more than 20% regression of maximum diameter of colon tumor in enhanced CT image will be randomly assigned to the Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody and continued with two more cycles of Capox chemotherapy along with the reduced dosage of Anti-PD-L1 monoclonal antibody and Clostridium butyricum. Then, these patients will receive curative surgery for colon cancer.

Drug: Oxaliplatin; Drug: Capecitabine; Drug: Anti-PD-L1 Monoclonal Antibody; Drug: Clostridium butyricum; Procedure: Colectomy

Interventions

Oxaliplatin DRUG

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.

Enhancement regimen of combined Anti-PD-L1 monoclonal antibody; Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody; Standard chemotherapy control cohort

Capecitabine DRUG

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.

Enhancement regimen of combined Anti-PD-L1 monoclonal antibody; Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody; Standard chemotherapy control cohort

Anti-PD-L1 Monoclonal Antibody DRUG

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.

Also known as: Envafolimab

Enhancement regimen of combined Anti-PD-L1 monoclonal antibody; Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody

Clostridium butyricum DRUG

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.

Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody

Colectomy PROCEDURE

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.

Enhancement regimen of combined Anti-PD-L1 monoclonal antibody; Enhancement regimen of combined lactobacillus and Anti-PD-L1 monoclonal antibody; Standard chemotherapy control cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

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

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Oxaliplatin; Capecitabine; envafolimab; phosphatidyltransferase, Clostridium butyricum; Colectomy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal 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; Surgical Procedures, Colorectal; Digestive System Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Jun Li, MD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY DIRECTOR

Central Study Contacts

Li Jun, MD

CONTACT

+86 13777878061; 2307016@zju.edu.cn

Jiao Yurong

CONTACT

+86 13732206364; jiaoyurong@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2023
• First Posted: June 22, 2023
• Study Start: August 1, 2023
• Primary Completion: August 1, 2025
• Study Completion (Estimated): August 1, 2030
• Last Updated: August 8, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)