Colorectal Cancer
Conditions
Keywords
Fluorouracil, Transendoscopic enteral tubing, Thermosensitive hydrogel, Colorectal Cancer
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.
Interventions
DRUGColonic local administration of fluorouracil with enhanced adhesion
Fluorouracil is administered via the colon as an injectable solution at a dose of 500 mg per day for 6 days, along with poloxamer 407 and poloxamer 188 used as thermosensitive hydrogel to enhance adhesion.
Sponsors
The Second Hospital of Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (according to RECIST1.1, investigator assessment) | One, three, and six months (or until conversion to surgery) after the initial treatment | Objective response rate (ORR) is defined as complete response (CR) and partial response (PR) proportion of participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | Every 3 months up to 24 months after the end of treatment | Overall survival (OS) is defined as the time from the first initiation of the study regimen to death from any cause time. |
| Disease control rate (according to RECIST1.1, investigator assessment) | One, three, and six months (or before conversion to surgery) after the initial treatment | Disease control rate (DCR) is defined as the proportion of participants with complete response (CR), partial response (PR) and stable disease (SD) × 100%. |
| Drop period to ensure operation resection | Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment | Drop period to ensure operation resection is defined as the proportion of participants whose tumors shrink following study induction therapy, thereby enhancing the safety and feasibility of surgical removal. |
| Progression-free survival | One, three, and six months (or until conversion to surgery) after the initial treatment | Progression-free survival (PFS) is defined as the time from the first initiation of study regimen treatment to the first imaging disease progression or the time of death, whichever occurs first. |
| Actual R0 resection rate | Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment | Actual R0 resection rate is defined as the proportion of participants who achieved R0 surgical resection after 4-6 courses of study induction therapy. |
| The incidence of treatment-related adverse events (AE) assessed by CTCAE, Version 5.0 | Throughout the treatment period and continuing for an additional 6 months after the treatment concludes, an average of 1 year | The severity of AE was graded as mild (grade 1), moderate (grade 2), severe/disabling (grade 3), life threatening (grade 4), and death (grade 5). All AE were divided in definitely, probably and possibly related to treatment. |
| Converted resection rate | Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment | Surgical conversion rate, defined as the proportion of participants who achieved gross complete resection after 4-6 courses of study induction therapy. |
Countries
China
Contacts
Primary ContactFaming Zhang, MD, PhD
Outcome results
None listed