Fluorouracil Treatment Via Colon for Colorectal Cancer

NCT06385418 | Recruiting Phase 2

• 1 other identifier: WST-CRC-202404
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Keywords

Fluorouracil; Transendoscopic enteral tubing; Thermosensitive hydrogel; Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (according to RECIST1.1, investigator assessment)

  Objective response rate (ORR) is defined as complete response (CR) and partial response (PR) proportion of participants.

  One, three, and six months (or until conversion to surgery) after the initial treatment

Secondary Outcomes (7)

• Progression-free survival

  One, three, and six months (or until conversion to surgery) after the initial treatment

• Overall survival

  Every 3 months up to 24 months after the end of treatment

• Disease control rate (according to RECIST1.1, investigator assessment)

  One, three, and six months (or before conversion to surgery) after the initial treatment

• Drop period to ensure operation resection

  Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment

• Converted resection rate

  Time from the first treatment to 4-6 cycles (each cycle is 28 days) of treatment

Study Arms (1)

Colonic local administration of fluorouracil with enhanced adhesion

EXPERIMENTAL

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.

Drug: Colonic local administration of fluorouracil with enhanced adhesion

Interventions

Colonic local administration of fluorouracil with enhanced adhesion DRUG

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.

Colonic local administration of fluorouracil with enhanced adhesion

Eligibility Criteria

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

You may qualify if:

• Chinese individuals aged 18 to 75 years, both male and female;
• Histologically confirmed diagnosis of colorectal cancer with measurable primary lesion according to RECIST 1.1;
• ECOG performance status ≤2;
• Expected survival of more than 3 months;
• Multidisciplinary team consensus that the patient is suitable for adding local chemotherapy to the established tumor treatment regimen;
• 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%;
• 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;
• Suitable physical condition and personal willingness to undergo colonic transendoscopic enteral tubing;
• Willingness to cooperate with physicians, and agree to regular follow-up visits and examinations as recommended after completion of treatment;
• Agreement to specimen collection and voluntary signing of a written informed consent form.

You may not qualify if:

• 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;
• Active severe clinical infections (≥ Grade 2 according to NCI-CTCAE version 5.0), including fungal, viral, or tuberculosis infections within the gastrointestinal tract;
• 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;
• History of immunodeficiency or other acquired or congenital immunodeficiency diseases, or history of organ transplantation;
• 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;
• Presence of other serious diseases that would render the subject ineligible for enrollment as determined by the investigator;
• Breastfeeding women;
• Known allergy or intolerance to the investigational drug or its excipients;
• Participation in another drug clinical trial within the past four weeks;
• Lack of legal capacity or restricted legal capacity.

Sponsors & Collaborators

• The Second Hospital of Nanjing Medical University: lead

Study Sites (1)

The Second Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210011, China

RECRUITING

Related Publications (9)

• Sun W, Zhang N, Li A, Zou W, Xu W. Preparation and evaluation of N(3)-O-toluyl-fluorouracil-loaded liposomes. Int J Pharm. 2008 Apr 2;353(1-2):243-50. doi: 10.1016/j.ijpharm.2007.11.017. Epub 2007 Nov 17.

  PMID: 18155370 BACKGROUND

• Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. doi: 10.1038/nrc1074.

  PMID: 12724731 BACKGROUND

• Liu G, Franssen E, Fitch MI, Warner E. Patient preferences for oral versus intravenous palliative chemotherapy. J Clin Oncol. 1997 Jan;15(1):110-5. doi: 10.1200/JCO.1997.15.1.110.

  PMID: 8996131 BACKGROUND

• Galandiuk S, Wrightson W, Marr L, Myers S, LaRocca RV. Suppository delivery of 5-fluorouracil in rectal cancer. Ann Surg Oncol. 1996 May;3(3):270-6. doi: 10.1007/BF02306282.

  PMID: 8726182 BACKGROUND

• Kulkarni R, Fanse S, Burgess DJ. Mucoadhesive drug delivery systems: a promising noninvasive approach to bioavailability enhancement. Part II: formulation considerations. Expert Opin Drug Deliv. 2023 Mar;20(3):413-434. doi: 10.1080/17425247.2023.2181332. Epub 2023 Feb 22.

  PMID: 36803264 BACKGROUND

• Zarrintaj P, Ramsey JD, Samadi A, Atoufi Z, Yazdi MK, Ganjali MR, Amirabad LM, Zangene E, Farokhi M, Formela K, Saeb MR, Mozafari M, Thomas S. Poloxamer: A versatile tri-block copolymer for biomedical applications. Acta Biomater. 2020 Jul 1;110:37-67. doi: 10.1016/j.actbio.2020.04.028. Epub 2020 May 15.

  PMID: 32417265 BACKGROUND

• Al Sabbagh C, Seguin J, Agapova E, Kramerich D, Boudy V, Mignet N. Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer. Eur J Pharm Biopharm. 2020 Dec;157:154-164. doi: 10.1016/j.ejpb.2020.10.011. Epub 2020 Oct 22.

  PMID: 33222768 BACKGROUND

• Seguin J, Pimpie C, Roy P, Al Sabbagh C, Pocard M, Mignet N, Boudy V. Combination of tumor cell anti-adhesion and anti-tumor effect to prevent recurrence after cytoreductive surgery in a mice model. Eur J Pharm Biopharm. 2021 Dec;169:37-43. doi: 10.1016/j.ejpb.2021.01.020. Epub 2021 Mar 14.

  PMID: 33727143 BACKGROUND

• Zhang F, Lu G, Wang X, Wu L, Li R, Nie Y. Concept, breakthrough, and future of colonic transendoscopic enteral tubing. Chin Med J (Engl). 2024 Mar 20;137(6):633-635. doi: 10.1097/CM9.0000000000003020. Epub 2024 Feb 7. No abstract available.

  PMID: 38321613 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

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

Study Officials

• Faming Zhang, MD, PhD

  Department of Microbiota Medicine & Medical Center for Digestive Diseases

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Faming Zhang, MD, PhD

CONTACT

86-025-58509883; fzhang@njmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice President

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: April 26, 2024
• Study Start: May 16, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

CN (1)