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Inulin

Fruquintinib: 4 mg/d, qd po, administered continuously for 2 weeks, discontinued for 1 week;

Fruquintinib

Sintilimab: 200 mg, i.v.gtt.D1, administered every 3 weeks;

Sintilimab

Inulin: 5g/d, qd po in the first week, 10g/d, bid po from the second week onwards.

Hongli Liu, PhD

Min Jin

This is a single-center exploratory clinical study to explore the efficacy and safety of Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer.

This was a prospective, two-arm, single-center, exploratory phase I study, randomized 2: 1 into an intervention group (Fruquintinib combined with Sintilimab and inulin group) and a control group (Fruquintinib combined with Sintilimab group). Fruquintinib: 4 mg/d, QD po, administered continuously for 2 weeks with a 1-week discontinuation; Sintilimab 200 mg, I.V., D1, administered every 3 weeks; Inulin: 5 g/d, qd po, in the first week, and 10 g/d, bid po, starting in the second week; Combination therapy was administered every 3 weeks as a treatment cycle. Combination therapy was administered until disease progression, death, or intolerable toxicity.

The study was divided into 3 phases: a screening phase, a treatment phase, and a follow-up phase. Tumor status was assessed using imaging methods every 6 weeks (±7 days) until disease progression (RECIST 1.1) or death (during patient treatment) or intolerable toxicity, and tumor treatment and survival status after disease progression were recorded. Safety observations included changes in AE, laboratory test values, vital signs, and electrocardiographic changes.

Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer

A Single-center Exploratory Clinical Study of Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer

Patients' dietary fiber intake was collected through dietary questionnaires, and the correlation with progression-free survival was calculated.

Total genomic DNA was extracted from the feces of all patients and metagenomic sequencing was performed. Alpha diversity and beta diversity were used to evaluate the diversity of intestinal microbiota. Abundance and taxonomic information were obtained through taxonomic annotation of the sequencing results.

Safety will be evaluated by incidence, severity and outcomes of adverse events (AEs) and categorized by severity in accordance with the NCI CTC AE Version 5.0.

was defined as the proportion of patients with the best overall assessment of complete or partial remission. 95% confidence intervals were calculated separately for each group rate using the Clopper-pearson method.

was defined as the time from enrollment to death from any cause. For patients whose death had not been reported at the time of analysis, the date of their last known survival was used as the censored date.

The time (in days) from patient enrollment to disease progression or death.

Disease control rate was defined as the proportion of patients whose best overall assessment was complete remission, partial remission, or stable disease.

The time interval from the onset of response (when CR or PR is first identified) to progression or death, whichever occurs.

Use LC-MS/MS to detect and quantify various substances including short-chain fatty acids, bile acids, organic acids, amino acids, sugars, flavonoids, nucleotides, steroid hormones and other substances in serum.

Luminex multi-factor liquid phase analysis technology is used to detect plasma cytokines. The detection indicators include IFN-γ, IL-6, IL-8, IL-10, IL-17A and TNF-α and other cytokines.

Use flow cytometry to detect the frequency of CD4 positive T cells, CD8 positive T cells, natural killer cells, regulatory T cells and other immune cells in peripheral blood.

Huazhong University of Science and Technology

Wuhan Union Hospital, China

Symptoms and General Pathology

Anastomotic Leak

Herbal and Botanical

Cola

Patients randomized to the intervention group will receive inulin supplementation for 14 days, preceding the surgery. Inulin will be given at a dosage of 10g/day divided in two doses.

Patients randomized to the control group will receive a placebo for 14 days, two times a day.

Inulin is a water soluble non-digestible carbohydrate, and it is available in more than 36,000 species of plants. It is often used as dietary fiber and has obtained the "Generally recognized as safe" status (GRAS) by the Food and Drug Administration (FDA).

Placebo

Carole Richard, MD

Nassima Taleb

Colorectal cancer (CRC) is the third most diagnosed cancer in Canada. The most common surgical procedure in patients with CRC is an intestinal resection followed by a reconnection to rejoin the ends of the remaining bowel. Among the postoperative complications, leaking of this intestinal connection is notably feared, affecting up to 20% of patients. These leaks are characterized by impaired intestinal healing and are associated with severe infections and even death.

Various studies have shown that gut microbiota, the bacteria that live in the digestive tract, plays an essential role in intestinal healing following surgery. These results support the possibility of enhancing intestinal healing through supplements that act as an energy source for gut bacteria. Indeed, animal studies have shown that inulin supplementation, a fiber commonly found in plants, improves intestinal healing following bowel surgery. However, no studies in humans have evaluated its effects on CRC surgery patients.

This study aims to determine feasibility of a randomized controlled trial that assesses the effects of inulin supplementation before elective colorectal surgery.

Based on preliminary data, our working hypotheses are that the gut microbiome plays a fundamental role in postoperative healing and that manipulation of preoperative microbiota using inulin will improve postoperative healing and prevent potential development of anastomotic leaks.

The pilot study aims to evaluate the feasibility of a randomized controlled trial that assesses the effects of inulin supplementation before elective colorectal surgery. The project has two main components, a clinical study, and a translational research. A randomized, multi-center, triple-blind, placebo-controlled clinical trial will be conducted to evaluate the impact of inulin supplementation on the clinical and oncological outcomes of inulin supplementation before elective colorectal oncological surgery. Mucosal, blood and fecal samples of patients with inulin supplementation will be compared with samples of patients without inulin supplementation.

The study objectives are:

1. Determine the tolerance of colorectal cancer patients to inulin supplementation before surgery.
2. Assess the effect of inulin supplementation on colonic healing and the rate of AL.
3. Determine the impact of inulin supplementation on the gut microbiota, the inflammatory markers, and the gut barrier function.
4. Assess the effect of inulin supplementation on CRC local and distant recurrence after surgery.

Identification of study participants

Patients who are about to undergo an oncological colorectal surgery will be recruited in the CHUM. Informed consent will be obtained from the patient before enrollment in the study.

Patients will be randomized to the inulin group (intervention group) or to the placebo group (control group). A stratified randomization will be conducted according to the sex (1- Male, 2-Female), the cancer location (1- Right and transverse colon, 2-Left colon and sigmoid, 3-Rectum) and the cancer grade.

Patients randomized to the intervention group will receive inulin supplementation for two weeks, preceding the surgery. Inulin will be given at a dosage of 10g/day divided in two doses. To foster compliance, the inulin will be provided in a calendar pill organizer. Patients randomized to the control group will receive a placebo for two weeks, twice a day. Placebo pills will be identical in appearance to the inulin pills. A total of 40 patients, 20 in each group, will be included in the pilot study.

Adequate colonic preparation will also be given to all the patients, including oral mechanical bowel preparation, oral antibiotics the day before surgery and intravenous antibiotics before surgical incision.

Collection of stool samples

Feces will be collected according to International Human Microbiome Standards (IHMS) guidelines (SOP 03). Two pre-operative specimens will be collected for each enrolled patient: pre-inulin/placebo supplementation and post-inulin/placebo supplementation.

Blood samples

Standard blood tests will be conducted for the participating patients. Supplementary volume will be collected during the per-operative test, before the surgery and at post-op day 3. Blood will be collected in two tubes to assess complete blood counts and to obtained serum.

Intraoperative mucosal sample

A mucosal biopsy coming from colonic anastomosis consist of a fragment from the transection line at the anastomosis. The specimen will be collected in a sterile tube and snap frozen.

Statistical Design

R, Stata and Prism will be used to perform the statistical analysis. Decision to use non-parametric tests is based on data normality (Shapiro-Wilk test) and homoscedasticity (Bartlett's test) tests. Multiple comparisons will be evaluated statistically by 1-way analysis of variance (ANOVA) or by Kruskal-Wallis test. Statistically significant differences will then be evaluated by two-tailed Student's t or Wilcoxon test. Multiple testing is corrected via False Discovery Rate estimation. For pre-supplementation and post-supplementation samples, a paired Student's t-test or paired Wilcoxon test will be used. For comparison of 2 groups, an unpaired Student's t-test or unpaired Wilcoxon test will be used.

The Effect of Inulin Supplementation on Colorectal Surgery Outcomes

The Effect of Inulin Supplementation on Colonic Healing and Surgical Outcomes Following Colorectal Surgery

The GSRS is a seven-point Likert-type scale with response options ranging from 1 (no discomfort at all) to 7 (very severe discomfort). It includes 15 questions that assess various gastrointestinal symptoms.

The DQLQ is a 9-item questionnaire that uses a seven-point Likert-type scale to assess the impact of gastrointestinal symptoms on quality of life. The response options range from 'never' to 'always'.

All patients presenting with suspicious clinical features, such as worrisome laboratory results, post-operative fever, or abnormal physical examination findings, will undergo radiological examinations to confirm an anastomotic leak.

The white blood cell count will be monitored on post-operative day 3 to check for signs of infection or inflammation.

The CRP will be monitored on post-operative day 3 to check for signs of infection or inflammation.

Changes in fecal calprotectin levels will be monitored to assess colonic inflammation.

MUC2 levels will assess the amount of mucin present in the mucosa, which is important for colonic healing after surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer	NCT06347198	Metastatic Colo...	Fruquintinib Sintilimab Inulin	18 Years - 75 Years	Wuhan Union Hospital, China
The Effect of Inulin Supplementation on Colorectal Surgery Outcomes	NCT05860322	Anastomotic Com...	Inulin Placebo	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer	NCT06347198	Metastatic Colo...	Fruquintinib Sintilimab Inulin	18 Years - 75 Years	Wuhan Union Hospital, China
The Effect of Inulin Supplementation on Colorectal Surgery Outcomes	NCT05860322	Anastomotic Com...	Inulin Placebo	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)

Spots Global Cancer Trial Database for inulin

Every month we try and update this database with for inulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for inulin

Every month we try and update this database with for inulin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for inulin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.