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

NCT06347198 | Unknown Early Phase 1

• 1 other identifier: 20230807-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer

Keywords

metastatic colorectal cancer; inulin; Sintilimab; Fruquintinib

Outcome Measures

Primary Outcomes (2)

• Intestinal microbiota diversity, abundance and taxonomic information

  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.

  6 months after the recruitment of the last subject.

• adverse events

  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.

  from the date of first dose to the 30 days post the last dose

Secondary Outcomes (8)

• Objective remission rate (ORR)

  6 months after the recruitment of the last subject.

• Overall survival (OS)

  from date of randomization until the date of progressive disease or EOT due to any cause, assessed up to 1 year

• Progression-free survival (PFS)

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

• Disease control rate (DCR)

  from date of randomization until the date of progressive disease or EOT due to any cause, assessed up to 1 year

• Duration of remission (DOR)

  from date of the first documentation of response to the date of the first documentation of objective tumor progression or death due to any cause, whichever came first, assessed up to 1 year

Other Outcomes (1)

• Correlation between dietary fiber intake and progression-free survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year

Study Arms (2)

Intervention group (Fruquintinib combined with Sintilimab and inulin group)

EXPERIMENTAL

Drug: Fruquintinib; Drug: Sintilimab; Drug: Inulin

Control group (Fruquintinib combined with Sintilimab group)

OTHER

Drug: Fruquintinib; Drug: Sintilimab

Interventions

Fruquintinib DRUG

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

Control group (Fruquintinib combined with Sintilimab group); Intervention group (Fruquintinib combined with Sintilimab and inulin group)

Sintilimab DRUG

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

Control group (Fruquintinib combined with Sintilimab group); Intervention group (Fruquintinib combined with Sintilimab and inulin group)

Inulin DRUG

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

Intervention group (Fruquintinib combined with Sintilimab and inulin group)

Eligibility Criteria

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

You may qualify if:

• Have been fully informed about the study and have voluntarily signed an informed consent form;
• Aged 18-75 years (inclusive of 18 and 75 years);
• Pathologically determined unresectable advanced metastatic colorectal cancer;
• Failure of prior second- and back-line standard therapy;
• pMMR or MSS;
• ECOG physical status score of 0-2;
• Expected survival ≥ 6 months;
• Need to have at least one measurable lesion with a maximum diameter of at least 10 mm as determined by spiral CT scanning and at least 20 mm as determined by conventional CT scanning (Criteria for Evaluation of Efficacy in Solid Tumors, i.e., RECIST version 1.1);
• The function of vital organs meets the following requirements (the use of any blood components and cell growth factors is not permitted within \*14d prior to enrollment): absolute neutrophil count ≥1.5×10\^9/L; platelets ≥75×10\^9/L; hemoglobin ≥90g/L; total bilirubin \<1.5 times ULN; ALT and/or AST \<1.5 times ULN, and for patients with liver metastases \<3 times ULN; serum creatinine \<1.5 times ULN; endogenous creatinine clearance ≥50 ml/min;
• Men and women of childbearing age need to use effective contraception;
• Not allergic to inulin;
• Subjects agree to provide sufficient blood and fecal samples for immune function and intestinal microbiology testing.

You may not qualify if:

• Inability to comply with the study protocol or study procedures;
• Prior treatment with a vascular endothelial growth factor receptor (VEGFR) inhibitor or prior treatment with an immune checkpoint inhibitor;
• Other malignancy within the past 5 years, except for basal or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
• The presence of central nervous system (CNS) metastases or previous brain metastases prior to enrollment
• autoimmune disease or history of autoimmune disease within 4 weeks prior to enrollment
• Previous allogeneic bone marrow transplantation or organ transplantation;
• Uncontrolled malignant ascites (defined as ascites that, in the judgment of the investigator, cannot be controlled by means of diuretics or puncture);
• Severe cardiovascular disease, including unstable angina or myocardial infarction, within 6 months prior to initiation of study treatment, clinically significant cardiovascular disease, including unstable angina or myocardial infarction, within 6 months prior to initiation of study treatment, including, but not limited to, acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months prior to enrollment; congestive Heart failure New York Heart Association (NYHA) classification \>2; Ventricular arrhythmia requiring pharmacologic treatment; LVEF (left ventricular ejection fraction) \<50%;
• Subjects with hypersensitivity to the study drug or any of its adjuvants;
• Have participated in a clinical trial of another drug not yet approved or marketed in China within 4 weeks prior to enrollment and have been treated with the corresponding trial drug;
• Electrolyte abnormalities of clinical significance as determined by the investigator;
• Pre-existing medically uncontrolled hypertension, defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg;
• The presence of poorly controlled diabetes mellitus (fasting glucose concentration ≥ CTCAE grade 2 after regular treatment) prior to enrollment;
• Any disease or condition that interferes with drug absorption prior to enrollment or the patient is unable to take Fruquintinib orally;
• The presence of gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, or active bleeding from unresected tumors prior to enrollment, or other conditions that may cause gastrointestinal bleeding or perforation, as determined by the investigator;

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Huazhong University of Science and Technology: collaborator

Study Sites (1)

Min Jin

Wuhan, Hubei, 430030, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; sintilimab; Inulin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Carbohydrates; Carbohydrates; Fructans; Polysaccharides

Central Study Contacts

Hongli Liu, PhD

CONTACT

+86-027-85871962; hongli_liu@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2024
• First Posted: April 4, 2024
• Study Start: April 10, 2024
• Primary Completion: December 1, 2024
• Study Completion: May 1, 2025
• Last Updated: April 4, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)