Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer
Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer: a Prospective Single-center Multi-arm Open-label Randomized Phase II Study
Second Affiliated Hospital, School of Medicine, Zhejiang University
100 participants
Aug 1, 2023
INTERVENTIONAL
Conditions
Summary
This study aims to elucidate the regression effects of neoadjuvant chemotherapy combined with immunotherapy and adjuvant therapy in locally advanced MSS colon cancer.
Eligibility
Inclusion Criteria7
- 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 Criteria13
- 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.
Interventions
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.
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.
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.
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.
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.
Locations(1)
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NCT05914389