Enrolling by invitation
Phase 4
Intestinal Microbiota Transplantation, Radiochemotherapy and Sintilimab in Localized Advanced Colon Cancer
Condition(s) studied
Localized Advanced Rectal Adenocarcinoma
Investigational drug(s) / intervention(s)
Sintilimab plus Chemotherapy: All patients received standard long-term radiation therapy (LCRT) (50.0Gy/25f) and concurrent chemotherapy with capecitabine (825 mg/m2, bid, po) (Phase 1); Xelox scheme (Oxaliplatin 130 mg/m2, ivgtt ，d1； Capecitabine 1000 mg/m2, bid，d1-14) (Phase 2); . During the radiotherapy and chemotherapy period, they also received two cycles of immunotherapy with Sintilimab (200mg, ivgtt, d1, q3w).
Intestinal microbiota capsules: During Phase 1, intestinal microbiota transplantation treatment, oral intestinal microbiota capsules are used for transplantation treatment, with a dose of 30 capsules/day (about 1U sediment microbiota, containing about 1 × 1013 bacteria). Transplantation is carried out continuously for 3 days starting from each week, for a total of 3 courses of treatment.
Standard Long Course Radiotherapy: 50.0Gy/25f
Total mesorectal excision: 6-8 weeks after the end of the first phase and combined with 5 cycles of Xelox regimen adjuvant chemotherapy.
Study summary
The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision. While Immune checkpoint inhibitors are promising in the treatment of various cancers, the combination of radiotherapy and immunotherapy still lacks high-level evidence-based medicine, and the efficacy is still limited in rectal cancer.
Thus, we designed a study on the efficacy and safety of intestinal microbiota transplantation combined with synchronous radiochemotherapy and immune checkpoint inhibitor xindilimab neoadjuvant therapy for locally advanced rectal cancer.
Eligibility
1. Must sign the informed consent form with good compliance;
2. Age 18 to 75 years ;
3. ECOG score 0-1 points;
4. Locally advanced rectal adenocarcinoma and TNM clinical stage IIA-IIIC (T3-4/N+);
5. The distance between the lower edge of the tumor and the anal margin is less than or equal to 10cm.
6. Have not received any anti-tumor treatment in the past (including but not limited to surgery, radiotherapy, chemotherapy, anti vascular therapy, immunotherapy, etc.); 7 The main organ functions well. -
Exclusion Criteria:
* 1\. Other malignant tumors, including rectal cancer with other pathological types within 5 years; 2. Not using probiotics in the past 2 months; 3. Severe damage to the intestinal barrier, such as sepsis, active gastrointestinal bleeding, perforation, etc.; 4. Weight loss of ≥ 20% within 90 days; 5. Poor nutritional status or PG-SGA score ≥ 9; 6. Severe and/or uncontrolled illnesses.
1. Poor blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg)
2. ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470ms), and ≥ grade 2 congestive heart failure
3. History of interstitial lung disease, non infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute lung diseases
4. Active or uncontrolled severe infection (≥ CTCAE level 2 infection)
5. Cirrhosis and active hepatitis; Active hepatitis (hepatitis B reference: HBsAg is positive, and the HBV DNA detection value exceeds the upper limit of normal value; Hepatitis C reference: HCV antibody positive and HCV virus titer detection value exceeding the upper limit of normal); Note: Subjects with positive hepatitis B B surface antigen or core antibody and patients with hepatitis C who meet the inclusion conditions need continuous antiviral treatment to prevent virus activation
6. Active syphilis patients
7. Renal failure requiring hemodialysis or peritoneal dialysis
8. History of immunodeficiency, including HIV positivity or other acquired or congenital immunodeficiency diseases, or organ transplantation 7. Poor control of diabetes (fasting blood glucose \[FBG\]\>10mmol/L) 8. Significant surgical treatment, open biopsy, or significant traumatic injury within 60 days prior to the start of treatment; Or long-term untreated wounds or fractures 9. Serious arterial/venous thrombotic events such as cerebrovascular accidents (including temporary ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism occurred within 6 months before the start of treatment 10. History of abuse of psychotropic drugs who are unable to quit or have mental disorders 11. History of severe allergies 12. Pregnant or lactating women
Primary outcome measure(s)
- pathologic complete response rate — Up to 12 weeks
Defined as the percentage of subjects with ypT0N0 who have no residual tumor cells in the primary tumor and lymph nodes after surgery compared to all subjects.
- Overall Survival — Three years after the end of treatment
The percentage of subjects who are still alive after 3 years of follow-up among all subjects.
- R0 resection rate — During the surgery
Defined as the complete resection rate of tumors with negative margins removed under a microscope
- Tumor regression grading — During the surgery
According to AJCC 8th edition, the Tumor regression grading is based on the proportion of fibrosis and residual tumors in the tumor. Grade 0 indicates complete regression of the tumor, Grade 1 indicates regression of over 90%, Grade 2 indicates regression between 10% and 90%, Grade 3 indicates regression of less than 10%, and Grade 4 indicates no significant regression of the tumor
- Completion rate of neoadjuvant therapy — Up to 6 weeks
Defined as the percentage of subjects who have completed all neoadjuvant therapies compared to all subjects
- Event free survival rate — Three years after the end of treatment
The percentage of subjects who were followed up for 3 years and still survived without disease recurrence or change of treatment plan among all subjects.
- Disease-free survival rate — Three years after the end of treatment
The percentage of subjects who were followed up for 3 years and still survived without disease recurrence among all subjects.
Trial sites (1)
| Facility | City | Region | Status |
|---|
| First Affiliated Hospital of Ningbo University |
Ningbo |
Zhejiang |
|
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