Localized Advanced Rectal AdenocarcinomaPhase 4NCT06931808
Intestinal Microbiota Transplantation, Radiochemotherapy and Sintilimab in Localized Advanced Colon Cancer
A Phase 4 study testing Sintilimab plus Chemotherapy, Intestinal microbiota capsules and Standard Long Course Radiotherapy in people with Localized Advanced Rectal Adenocarcinoma, run by First Affiliated Hospital of Ningbo University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Localized Advanced Rectal Adenocarcinoma
- What is being tested?
- Sintilimab plus Chemotherapy, Intestinal microbiota capsules and Standard Long Course Radiotherapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2025to 1 Aug 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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.
- Poor blood pressure control (systolic blood pressure ≥ 150mmHg or diastolic blood pressure ≥ 100mmHg)
- ≥ grade 2 myocardial ischemia or myocardial infarction, arrhythmia (QTc ≥ 470ms), and ≥ grade 2 congestive heart failure
- History of interstitial lung disease, non infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute lung diseases
- Active or uncontrolled severe infection (≥ CTCAE level 2 infection)
- 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
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- Active syphilis patients
- Renal failure requiring hemodialysis or peritoneal dialysis
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
First Affiliated Hospital of Ningbo University
Ningbo, Zhejiang, 315000
About this study
Official title: The Efficacy and Safety of Intestinal Microbiota Transplantation Combined With Radiochemotherapy and Sintilimab in Neoadjuvant Treatment for Locally Advanced Rectal cancer-a Single Arm, Prospective, Single Center Exploratory Study
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.
Read the detailed description
The incidence rate of colorectal cancer (CRC) ranks among the top three most common cancers in the world, while the mortality rate ranks among the top two. Early symptoms of rectal cancer are not obvious, and about 60% of patients are diagnosed with locally advanced rectal cancer. The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision. However, the response of patients to radiotherapy showed significant heterogeneity, with pathological complete response rates (pCR) ranging from 6% to 39%. In addition, a significant proportion of LARC patients (20% -40%) do not respond to preoperative radiotherapy (preRT). Therefore, it is crucial to find ways to alleviate radiation resistance within tumors.
Immune checkpoint inhibitors (ICIs) are increasingly being used in various solid tumors. However, immunotherapy in the field of CRC has always been distinct, with patients with mismatch repair defects (dMMR) or high microsatellite instability (MSI-H) (accounting for 5% -15% of all CRCs) having a higher tumor mutation burden (TMB) and more tumor infiltrating lymphocytes (TILs), making them the absolute dominant population for immunotherapy; However, patients with microsatellite stability (MSS) or normal mismatch repair (pMMR) have poor immune therapy efficacy. At present, radiotherapy is widely regarded as a mechanism that triggers local and systemic immune responses, providing a theoretical basis for the combination of radiotherapy and immunotherapy (iRT). In 2022, the VOLTAGE-A study reported the addition of nivolumab treatment after long-term synchronous chemoradiotherapy. The results showed that the major pathological response (MPR) rate and pCR rate in 37 MSS LARC patients after surgery were 38% and 30%, respectively. In addition, multiple studies have conducted similar explorations with different methods. Overall, these studies have achieved certain therapeutic effects, with pCR rates ranging from 37.5% to 57.1%. However, the combination of radiotherapy and immunotherapy still lacks high-level evidence-based medicine, and the efficacy is still limited.
The gut microbiota is a complex microbial community closely related to the occurrence and development of rectal cancer. Previous studies have shown that gut microbiota can predict response to neoadjuvant radiotherapy, improve treatment response, and reduce treatment toxicity. In addition, it has been confirmed that the gut microbiota can reshape the tumor immune microenvironment (TiME), thereby affecting the response to ICIs. The results of two Phase I trials indicate that gut microbiota transplantation (FMT) derived from responders effectively reversed immune resistance in melanoma, laying the foundation for the clinical application of FMT in cancer immunotherapy. In a phase II study, a total of 20 MSS mCRC patients were enrolled and received FMT combined with trastuzumab and furosemide as third line or above treatment. The median PFS was 9.6 months (95% CI 4.1-15.1) and the median OS was 13.7 months (95% CI 9.3-17.7), with controllable side effects, demonstrating the potential of FMT in the field of rectal cancer.
- Conditions
- Localized Advanced Rectal Adenocarcinoma
- Being tested
- Sintilimab plus Chemotherapy, Intestinal microbiota capsules, Standard Long Course Radiotherapy, Total mesorectal excision
- Keywords
- mid-low position, IIA-IIIC (T3-4/N+)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sintilimab plus ChemotherapyDrug
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 capsulesDrug
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 RadiotherapyRadiation
50.0Gy/25f
Total mesorectal excisionProcedure or surgery
6-8 weeks after the end of the first phase and combined with 5 cycles of Xelox regimen adjuvant chemotherapy.
| Study group | Role | What they receive |
|---|---|---|
| Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab | Experimental | Intestinal microbiota transplantation combined with synchronous radiotherapy, chemotherapy, and Sintilimab as neoadjuvant therapy Receives: Drug: Sintilimab plus Chemotherapy; Drug: Intestinal microbiota capsules; Radiation: Standard Long Course Radiotherapy; Procedure: Total mesorectal excision |
What is being measured
The primary outcome is the main question the study is designed to answer.
pathologic complete response rate
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.
Measured: Up to 12 weeks
Overall Survival
The percentage of subjects who are still alive after 3 years of follow-up among all subjects.
Measured: Three years after the end of treatment
R0 resection rate
Defined as the complete resection rate of tumors with negative margins removed under a microscope
Measured: During the surgery
Tumor regression grading
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
Measured: During the surgery
Completion rate of neoadjuvant therapy
Defined as the percentage of subjects who have completed all neoadjuvant therapies compared to all subjects
Measured: Up to 6 weeks
Event free survival rate
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.
Measured: Three years after the end of treatment
Disease-free survival rate
The percentage of subjects who were followed up for 3 years and still survived without disease recurrence among all subjects.
Measured: Three years after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2025
- Study start1 Mar 2025
- Primary completion1 Mar 2026 (estimated)
- Study completion1 Aug 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Localized Advanced Rectal AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital of Ningbo University
- Sponsor type
- Research network
- Responsible party
- Principal investigator, Qingsong Tao, First Affiliated Hospital of Ningbo University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06931808
- Sponsor's protocol ID
- KY-XM-038
- Status last verified
- Apr 2025
- First submitted
- 15 Mar 2025
- Last updated
- 17 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Efficacy and Safety of Intestinal Microbiota Transplantation Combined With Radiochemotherapy and Sintilimab in Neoadjuvant Treatment for Locally Advanced Rectal cancer-a Single Arm, Prospective, Single Center Exploratory Study
- ClinicalTrials.gov ID
- NCT06931808
- Acronym / sponsor ID
- KY-XM-038
- Conditions
- Localized Advanced Rectal Adenocarcinoma
- Keywords
- mid-low position, IIA-IIIC (T3-4/N+)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- First Affiliated Hospital of Ningbo UniversityResearch network
- Study start
- 1 Mar 2025 (actual)
- Primary completion
- 1 Mar 2026 (estimated)
- Study completion
- 1 Aug 2028 (estimated)
- First posted
- 17 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The incidence rate of colorectal cancer (CRC) ranks among the top three most common cancers in the world, while the mortality rate ranks among the top two. Early symptoms of rectal cancer are not obvious, and about 60% of patients are diagnosed with locally advanced rectal cancer. The standard treatment for locally advanced rectal cancer is neoadjuvant chemoradiotherapy followed by total mesorectal excision. However, the response of patients to radiotherapy showed significant heterogeneity, with pathological complete response rates (pCR) ranging from 6% to 39%. In addition, a significant proportion of LARC patients (20% -40%) do not respond to preoperative radiotherapy (preRT). Therefore, it is crucial to find ways to alleviate radiation resistance within tumors.
Immune checkpoint inhibitors (ICIs) are increasingly being used in various solid tumors. However, immunotherapy in the field of CRC has always been distinct, with patients with mismatch repair defects (dMMR) or high microsatellite instability (MSI-H) (accounting for 5% -15% of all CRCs) having a higher tumor mutation burden (TMB) and more tumor infiltrating lymphocytes (TILs), making them the absolute dominant population for immunotherapy; However, patients with microsatellite stability (MSS) or normal mismatch repair (pMMR) have poor immune therapy efficacy. At present, radiotherapy is widely regarded as a mechanism that triggers local and systemic immune responses, providing a theoretical basis for the combination of radiotherapy and immunotherapy (iRT). In 2022, the VOLTAGE-A study reported the addition of nivolumab treatment after long-term synchronous chemoradiotherapy. The results showed that the major pathological response (MPR) rate and pCR rate in 37 MSS LARC patients after surgery were 38% and 30%, respectively. In addition, multiple studies have conducted similar explorations with different methods. Overall, these studies have achieved certain therapeutic effects, with pCR rates ranging from 37.5% to 57.1%. However, the combination of radiotherapy and immunotherapy still lacks high-level evidence-based medicine, and the efficacy is still limited.
The gut microbiota is a complex microbial community closely related to the occurrence and development of rectal cancer. Previous studies have shown that gut microbiota can predict response to neoadjuvant radiotherapy, improve treatment response, and reduce treatment toxicity. In addition, it has been confirmed that the gut microbiota can reshape the tumor immune microenvironment (TiME), thereby affecting the response to ICIs. The results of two Phase I trials indicate that gut microbiota transplantation (FMT) derived from responders effectively reversed immune resistance in melanoma, laying the foundation for the clinical application of FMT in cancer immunotherapy. In a phase II study, a total of 20 MSS mCRC patients were enrolled and received FMT combined with trastuzumab and furosemide as third line or above treatment. The median PFS was 9.6 months (95% CI 4.1-15.1) and the median OS was 13.7 months (95% CI 9.3-17.7), with controllable side effects, demonstrating the potential of FMT in the field of rectal cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab | Experimental | Drug: Sintilimab plus Chemotherapy, Drug: Intestinal microbiota capsules, Radiation: Standard Long Course Radiotherapy, Procedure: Total mesorectal excisionIntestinal microbiota transplantation combined with synchronous radiotherapy, chemotherapy, and Sintilimab as neoadjuvant therapy |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sintilimab plus ChemotherapyAll 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). | Drug | Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab |
| Intestinal microbiota capsulesDuring 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. | Drug | Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab |
| Standard Long Course Radiotherapy50.0Gy/25f | Radiation | Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab |
| Total mesorectal excision6-8 weeks after the end of the first phase and combined with 5 cycles of Xelox regimen adjuvant chemotherapy. | Procedure or surgery | Intestinal microbiota transplantation combined with chemoradiotherapy and Sintilimab |
Primary outcome
pathologic complete response rate
Time frame: 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
Time frame: 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
Time frame: During the surgery
Defined as the complete resection rate of tumors with negative margins removed under a microscope
Tumor regression grading
Time frame: 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
Time frame: Up to 6 weeks
Defined as the percentage of subjects who have completed all neoadjuvant therapies compared to all subjects
Event free survival rate
Time frame: 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
Time frame: 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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2025.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sintilimab plus Chemotherapy, Intestinal microbiota capsules and Standard Long Course Radiotherapy in people with Localized Advanced Rectal Adenocarcinoma, run by First Affiliated Hospital of Ningbo University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pathologic complete response rate (time frame: Up to 12 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025; AzTrials last refreshed its copy on 8 Nov 2026.