Trial Title:
Oral Inulin in Combination With Fruquintinib Plus Sintilimab as Third- or Further-line Treatment in Metastatic Colorectal Cancer
NCT ID:
NCT06347198
Condition:
Metastatic Colorectal Cancer
Conditions: Official terms:
Colorectal Neoplasms
Conditions: Keywords:
metastatic colorectal cancer
inulin
Sintilimab
Fruquintinib
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Fruquintinib
Description:
Fruquintinib: 4 mg/d, qd po, administered continuously for 2 weeks, discontinued for 1
week;
Arm group label:
Control group (Fruquintinib combined with Sintilimab group)
Arm group label:
Intervention group (Fruquintinib combined with Sintilimab and inulin group)
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
Sintilimab: 200 mg, i.v.gtt.D1, administered every 3 weeks;
Arm group label:
Control group (Fruquintinib combined with Sintilimab group)
Arm group label:
Intervention group (Fruquintinib combined with Sintilimab and inulin group)
Intervention type:
Drug
Intervention name:
Inulin
Description:
Inulin: 5g/d, qd po in the first week, 10g/d, bid po from the second week onwards.
Arm group label:
Intervention group (Fruquintinib combined with Sintilimab and inulin group)
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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;
- Patients with evidence or history of significant bleeding tendency within 3 months
prior to enrollment (bleeding >30 mL within 3 months, vomiting blood, black stool,
blood in stool), hemoptysis (>5 mL of fresh blood within 4 weeks), or a
thromboembolic event (including stroke events and/or transient ischemic attack)
within 12 months;
- Active or uncontrolled serious infection (≥ CTCAE v5.0 grade 2 infection);
- Known human immunodeficiency virus (HIV) infection. Known history of clinically
significant liver disease, including viral hepatitis [known hepatitis B virus (HBV)
carriers must be excluded from active HBV infection, i.e., HBV DNA-positive (>1×10^4
copies/mL or >2000 IU/ml); known hepatitis C virus infection (HCV) and HCV
RNA-positive (>1×10^3 copies/mL)];
- Unresolved toxic reactions above CTCAE v5.0 Grade 1 or higher due to any prior
anticancer therapy, excluding alopecia, lymphopenia, and neurotoxicity ≤ Grade 2 due
to oxaliplatin;
- Females who are pregnant (positive pregnancy test prior to dosing) or breastfeeding;
- Transfusion therapy, blood products, and hematopoietic factors, such as albumin and
granulocyte colony-stimulating factor (G-CSF), received within 14 days prior to
enrollment;
- Any other disease with clinically significant metabolic abnormalities, physical
examination abnormalities, or laboratory test abnormalities that, in the judgment of
the investigator, give reason to suspect that the patient has a disease or condition
for which the use of the study medication is inappropriate (e.g., has epileptic
seizures that require treatment), or that would interfere with the interpretation of
the study results, or that would place the patient at a high level of risk
- Those with routine urinalysis suggestive of urinary protein ≥2+ and a 24-hour urine
protein volume >1.0 g;
- Complications requiring long-term immunosuppressive therapy or requiring systemic or
topical immunosuppressive corticosteroids (>10 mg/day prednisone or other
therapeutic hormones);
- Use of antibiotics or probiotic preparations (probiotic candies, powders, pills,
probiotic juices, probiotic yogurts, oligosaccharides, etc.) within the last month
- Patients who, in the opinion of the investigator, are not suitable for enrollment in
this study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Min Jin
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Recruiting
Contact:
Last name:
Min Jin
Phone:
18807108606
Email:
minjin86@126.com
Start date:
April 10, 2024
Completion date:
May 1, 2025
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Collaborator:
Agency:
Huazhong University of Science and Technology
Agency class:
Other
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06347198
