Clinical trial NCT06801665: FMT+ QL1706+bevacizumab+ XELOX As First-line Treatment for Advanced MSS-type Colon Cancer with Liver Metastasis
Official title: Fecal Microbiota Transplantation Combined with QL1706, Bevacizumab, and XELOX As First-line Treatment for Advanced MSS-type Colon Cancer with Liver Metastasis: a Prospective, Multi-center, Single-arm Phase II Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Colon Cancer Liver Metastases
Lead sponsor: Changzhou No.2 People's Hospital
Sponsor class: OTHER
First posted: 2025-01-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators plan to initiate a prospective, multicenter, phase II study, recruiting 30 patients with advanced colon cancer patients with liver metastasis who have not received prior treatment. This study plans to reconstruct intestinal microecology through fecal microbiota transplantation (FMT), and combine with QL1706+Bevacizumab+XELOX to enhance the anti-tumor immune effect at the same time, thereby improving the prognosis of colon cancer patients with liver metastasis.

Detailed description: This is a prospective, single-arm, multi-center, exploratory clinical study. Patients with previously untreated, newly diagnosed advanced colon cancer with liver metastasis, who could be diagnosed by histological or cytological means, ECOG PS 0-1, excluded Ras, Raf wild type left colon and rectum, excluded dMMR/MSI-H. Eligible subjects who met the inclusion criteria were screened and signed informed consent.

FMT was performed 2 days before treatment with QL1706, bevacizumab, and chemotherapy. QL1706， bevacizumab, and chemotherapy (XELOX) were administered every 3 weeks according to the patient's body surface area. A total of 6 cycles were performed. Subsequent maintenance therapy was at the discretion of the investigator.

RECIST v1.1 was used for tumor evaluation every 6 weeks during treatment. NCI-CTCAE 5.0 was used for safety assessment every 3 weeks. Adverse events were recorded throughout the study to 90 days after the end of treatment. Treatment continues until disease progression, subject withdraws informed consent, loss of follow-up, or death. Patients should provide 10ml whole blood samples and fecal samples at baseline, after two cycles of treatment, after four cycles of treatment, before maintenance treatment for the detection of efficacy prediction markers (each cycle is 21 days).

Eligibility criteria: Inclusion Criteria:

1. Histological or cytological confirmed advanced colon cancer with liver metastasis.
2. Signed written informed consent.
3. Have not received anti-tumor treatment.
4. According to the investigators assessment, at least one measurable target lesion defined by RECIST v1.1.
5. Patients of both sexes, aged ≥18 years and ≤75 years.
6. ECOG PS 0-1;
7. Expected survival time ≥ 3 months;
8. Have adequate organ and bone marrow function, laboratory examination within 7 days prior to enrollment meets the following requirements, as follows:

1) Blood routine: ANC ≥ 1.5 × 10\^9/L, Platelet count ≥ 100 × 10\^9/L, HGB ≥100 g/L (no blood transfusion or erythropoietin dependence within 14 days); 2) Liver function: TBIL ≤1.5 x ULN; ALT/AST ≤ 5 x ULN; ALP ≤5×ULN; 3) Renal function: Cr ≤1.5×ULN, or creatinine clearance ≥50 mL/min: Urine routine results showed urinary protein \< 2+; 4) Coagulation function: INR or PT ≤1.5 x ULN. 9.For female subjects of reproductive age, a urine or serum pregnancy test should be performed and the result is negative 3 days prior to receiving the initial study drug administration.

10. For women of childbearing potential (WOCBP): agreement to refrain from heterosexual intercourse or use contraception.

11. For men: agreement to refrain from heterosexual intercourse or use a condom, and agreement to refrain from donating sperm.

Exclusion Criteria:

1. Suffered from other malignancies in the past 5 years, excluding cured basal cell carcinoma of the skin, cervical carcinoma in situ and papillary thyroid carcinoma.
2. Patients requiring elective surgery during the trial.
3. Patients who cannot take oral drugs, or have conditions that the investigator determines to significantly affect gastrointestinal absorption, such as chronic diarrhea, intestinal obstruction, etc., and are not suitable for treatment.
4. Patients during pregnancy (positive pregnancy test) or lactation.
5. Central nervous system metastasis or meningeal metastasis.
6. Uncontrollable bone metastasis, or patients at risk of fracture, requiring surgery, local radiation therapy.
7. Patients with active infection requiring systemic anti-infection treatment.
8. Patients with a history of immunodeficiency, including those who are positive for HIV antibody tests.
9. Patients with known, active autoimmune diseases.
10. Patients with uncontrolled active hepatitis B, patients with hepatitis C virus infection (HCV antibody positive).
11. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to: severe arrhythmia, acute coronary syndrome within 6 months, congestive heart failure, aortic dissection, stroke, and T IA history.
12. Severe bleeding events occur within half a year, or high bleeding risk factors such as active digestive tract ulcers and esophageal and gastric varices due to liver cirrhosis.
13. Patients with diabetes who cannot be stably controlled by drugs (including insulin).
14. Mental or language disorders that prevent communication with the patient;
15. Patients participating in another clinical trial.
16. MSI-H/ d MMR without immunotherapy; left colorectum of Ras, Raf wild-type.
17. The investigator believes that the subject has other serious systemic diseases or other conditions that make him unsuitable for participation in this trial.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 24 months
Secondary outcomes:
measure: Median Progression-Free Survival (mPFS)
timeFrame: up to 24 months
measure: Median Overall Survival (mOS)
timeFrame: up to 24 months
measure: 6-Months Progression-Free Survival Rate (6month-PFS)
timeFrame: up to 6 months
measure: 12-Months Progression-Free Survival Rate (12month-PFS)
timeFrame: up to 12 months
measure: 18-Months Progression-Free Survival Rate (18month-PFS)
timeFrame: up to 18 months
measure: 6-Months overall survival rate(6-Months-OS Rate)
timeFrame: up to 6 months
measure: 12-Months overall survival rate(12-Months-OS Rate)
timeFrame: up to 12 months
measure: 18-Months overall survival rate(18-Monthsr-OS Rate)
timeFrame: up to 18 months
measure: Objective Response Rate (ORR) of liver metastases
timeFrame: up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: up to 24 months
measure: Surgical conversion rate
timeFrame: up to 24 months
measure: Incidence of Adverse events (AEs)
timeFrame: up to 24 months
measure: Quality of Life (QoL)
timeFrame: up to 24 months
measure: The Diversity of Fecal Microbiota
timeFrame: up to 24 months
Other outcomes:
Locations:
Study officials:
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