NCT06783491

Efficacy of the Use of Neoadjuvant With/Without Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Colon Cancer

Efficacy of the Use of Neoadjuvant With/Without Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Colon Cancer: A Phase III Multi-arm, Randomized and Controlled Clinical Trial (FOXHIPECT4)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,083 (estimated)
• Sponsor: Maimónides Biomedical Research Institute of Córdoba · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The main objective of this randomized and controlled trial is to determine whether the use of a proactive strategy, systemic neoadjuvant treatment (FOLFOX) with or without hyperthermic intraperitoneal chemoterapy (HIPEC) with mitomycin C followed by postoperative systemic adjuvant treatment, increases disease-free survival at 36 months in patients with locally advanced colon cancer compared to standard treatment. Therefore, a phase III, randomized, academic, multicenter, controlled trial will be conducted. Patients with locally advanced colon adenocarcinoma (cT4, cT3 with invasion \>5mm) Nx and no metastases will be included. Control group (n=361) will receive standard treatment (surgery and adjuvant chemotherapy FOLFOX x 12 based); Experimental group 1 (n=361) = Neoadjuvant chemotherapy (FOLFOX x6) + surgery (associating HIPEC) and FOLFOX x 6; Experimental group 2 (n=361): Neoadjuvant chemotherapy (FOLFOX x6) + surgery and FOLFOX x 6. Randomization will be 1:1:1, stratified and centralized. The primary outcome will be disease-free survival at 36 months. Secondary outcomes will be tumor regression rate, ctDNA negativization, peritoneal relapse rate at 36 months, pattern of relapse, toxicity, morbidity and overall survival. Considering the results obtained with these two independent strategies (FOLFOX and HIPEC), a new trial is justified in order to provide strong evidence for this proactive treatment. The aim is to combine both to obtain a better benefit, which opens the direct possibility of increasing the current percentage of disease-free survival. The results of this study will have important scientific and social impact, since is aimed at improving the outcomes of one subpopulation of patients with locally advanced colon cancer whose current treatment, is not enough to avoid the recurrence of disease.

Detailed description

he MAIN HYPOTHESIS of this trial is that the combination of systemic neoadjuvant chemotherapy with hyperthermic intraperitoneal chemotherapy (HIPEC) will have a synergistic effect in preventing disease recurrence (at all levels) in patients with locally advanced colorectal cancer. Therefore, the GENERAL OBJECTIVE of this study is to determine whether the use of proactive systemic neoadjuvant treatment (FOLFOX) with or without HIPEC with mitomycin C followed by post-surgical systemic adjuvant treatment increases disease-free survival at 36 months in patients with locally advanced colon cancer compared to standard treatment. To achieve this general goal, we will implement the following specific objectives (SO): SO1: To determine the efficacy of neoadjuvant systemic treatment with or without HIPEC association disease-free survival (DFS) at 36 months. SO2: To conduct a stratified analysis by factors including tumor location (right/left), definitive pathologic stage II/III (high risk), sex and age. SO3: To evaluate tumor regression after neoadjuvant treatment using the Dworak tumor regression scale (grade 0-no regression to grade 5-total response). SO4: To evaluate the R0 surgery rate in the different treatment groups. SO5: To compare the circulating tumor DNA (ctDNA) detected after surgery in both, experimental and control groups and analyze its impact in survival according to its detection. SO6: To evaluate the morbidity and toxicity in the different treatment groups. SO7: To determine the efficacy of neoadjuvant systemic treatment with or without HIPEC association in peritoneal (local or diffuse) recurrence-free survival (PFS) at 36 months. SO8: To evaluate the effect of neoadjuvant therapy associated with HIPEC compared to neoadjuvant treatment on the pattern of disease recurrence.

Conditions

• Locally Advanced Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Mitomycin (MM)	Mitomycin 30mg/m2/4 litres of perfusion liquid (dextrose 1.5%). Single intraoperative dose.
DRUG	FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)	FOLFOX6 consists in oxaliplatin 85 mg/m2 iv. on day 1, 5FU 400 mg/m2 iv. in bolus followed by 2400 mg/m2 in a continuous infusion for 46 hours. Leucovorin: 400mg/m2 folinic acid (racemid dl) in a continuous infusion for 2 hours. Repeat every 2 weeks. Haematological recovery to ANC \>1.5x109/L and platelets \>75x109/L should be ensured prior to Day 1 of each 14-day cycle.
PROCEDURE	Cytoreductive surgery	Cytoreductive surgery will be defined as complete tumour resection including oncologic colectomy and adjacent structures with suspicious of infiltration to achieve a R0, bilateral oophorectomy is recommended in post-menopausal women

Timeline

• Start date: 2025-12-31
• Primary completion: 2030-06-01
• Completion: 2030-12-31
• First posted: 2025-01-20
• Last updated: 2025-11-24

Locations

1 site across 1 country: Spain