Clinical trial NCT06385418: Fluorouracil Treatment Via Colon for Colorectal Cancer
Official title: Fluorouracil Treatment Via Colon for Colorectal Cancer: an Exploratory Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Fluorouracil
Transendoscopic enteral tubing
Thermosensitive hydrogel
Colorectal Cancer
Lead sponsor: The Second Hospital of Nanjing Medical University
Sponsor class: OTHER
First posted: 2024-04-26
Enrollment: 40
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: Fluorouracil (5-FU) is a commonly used drug for colorectal cancer (CRC). Thermosensitive hydrogel presents a promising carrier for 5-FU to address challenges encountered with traditional administration methods. We propose an integrated approach utilizing colonic transendoscopic enteral tubing to cover the entire colon flexibly, coupled with a thermo-sensitive gel to enhance the adhesion of 5-FU. This clinical trial aims to assess the feasibility, safety, and efficacy of this approach for treating CRC.


Eligibility criteria: Inclusion Criteria:

1. Chinese individuals aged 18 to 75 years, both male and female;
2. Histologically confirmed diagnosis of colorectal cancer with measurable primary lesion according to RECIST 1.1;
3. ECOG performance status ≤2;
4. Expected survival of more than 3 months;
5. Multidisciplinary team consensus that the patient is suitable for adding local chemotherapy to the established tumor treatment regimen;
6. Adequate organ function meeting the following criteria: (1) Absolute neutrophil count ≥1.5 × 10\^9/L, platelets ≥100 × 10\^9/L, hemoglobin ≥90 g/L; (2) Total bilirubin ≤1.5 times the upper limit of normal (patients with biliary drainage via retrograde techniques included); ALT and AST ≤5 times the upper limit of normal, and for patients with liver metastases, serum total bilirubin less than or equal to 3 times the upper limit of the normal reference range; (3) Creatinine \<120 μmol/L, or MDRD estimated glomerular filtration rate \>60 mL/min; (4) Doppler echocardiography assessment: Left ventricular ejection fraction (LVEF) ≥50%;
7. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days before enrollment, and sexually active men or women agree to use appropriate contraception during the trial and for 8 weeks after the last dose of investigational drug;
8. Suitable physical condition and personal willingness to undergo colonic transendoscopic enteral tubing;
9. Willingness to cooperate with physicians, and agree to regular follow-up visits and examinations as recommended after completion of treatment;
10. Agreement to specimen collection and voluntary signing of a written informed consent form.

Exclusion Criteria:

1. Uncontrolled cardiovascular diseases, such as congestive heart failure (NYHA III-IV), coronary artery disease, cardiomyopathy, arrhythmias, or hemodynamic instability at enrollment, with a risk of significant events during the treatment period;
2. Active severe clinical infections (≥ Grade 2 according to NCI-CTCAE version 5.0), including fungal, viral, or tuberculosis infections within the gastrointestinal tract;
3. Coagulation abnormalities with bleeding tendencies (who do not meet the criteria of having a normal INR without the use of anticoagulants within 14 days prior to enrollment). Participants receiving anticoagulants or vitamin K antagonists such as warfarin or heparin are excluded unless their international normalized ratio (INR) is ≤1.5, with allowance for low-dose warfarin (1 mg orally once daily) or low-dose aspirin (daily dose not exceeding 100 mg) for prophylaxis;
4. History of immunodeficiency or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
5. Known progressive or actively treated other malignancies requiring intervention, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or cervical carcinoma in situ;
6. Presence of other serious diseases that would render the subject ineligible for enrollment as determined by the investigator;
7. Breastfeeding women;
8. Known allergy or intolerance to the investigational drug or its excipients;
9. Participation in another drug clinical trial within the past four weeks;
10. Lack of legal capacity or restricted legal capacity.

Primary outcomes:
measure: Objective response rate (according to RECIST1.1, investigator assessment)
timeFrame: One, three, and six months (or until conversion to surgery) after the initial treatment
Secondary outcomes:
measure: Progression-free survival
timeFrame: One, three, and six months (or until conversion to surgery) after the initial treatment
measure: Overall survival
timeFrame: Every 3 months up to 24 months after the end of treatment
measure: Disease control rate (according to RECIST1.1, investigator assessment)
timeFrame: One, three, and six months (or before conversion to surgery) after the initial treatment
measure: Drop period to ensure operation resection
timeFrame: Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment
measure: Converted resection rate
timeFrame: Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment
measure: Actual R0 resection rate
timeFrame: Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment
measure: The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0
timeFrame: Throughout the treatment period and continuing for an additional 6 months after the treatment concludes, an average of 1 year
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The Second Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Department of Microbiota Medicine & Medical Center for Digestive Diseases
name: Faming Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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