Efficacy of the Use of Neoadjuvant With/Without Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Locally Advanced Colon Cancer
FOXHIPECT4
2 other identifiers
interventional
1,083
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Dec 2025
Longer than P75 for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 8, 2025
CompletedFirst Posted
Study publicly available on registry
January 20, 2025
CompletedStudy Start
First participant enrolled
December 31, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2030
November 24, 2025
November 1, 2025
4.4 years
January 8, 2025
November 21, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Disease-free survival absolute
Absolute disease-free survival in months. The event will be defined by patient death from any cause or tumour recurrence
36 months after treatment.
Disease-free survival probability
Tumour disease-free survival at 3 years of follow-up (%). The event will be defined by patient death from any cause or tumour recurrence up to 36 months after treatment.
36 months after treatment.
Secondary Outcomes (6)
Absolute Overall survival
36 months after treatment.
Probability overall survival
36 months after treatment.
Tumour regression
12 weeks after treatment
ctDNA rate
36 months after treatment.
Absolute Disease-free survival in subgroups
36 months after treatment.
- +1 more secondary outcomes
Study Arms (3)
FOLFOX+SURGERY+HIPEC
EXPERIMENTALFOLFOX x6 (12 weeks) followed by cytoreductive surgery + HIPEC (mitomycin 30mg/m2 for 60 min) followed by FOLFOX x6 (12 weeks).
FOLFOX+SURGERY
EXPERIMENTALFOLFOX x6 (12 weeks) followed by cytoreductive surgery followed by FOLFOX x6 (12 weeks).
cytoreductive surgery + standard care
ACTIVE COMPARATORcytoreductive surgery followed by standard care (adjuvant therapy according to local protocol). 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.
Interventions
Mitomycin 30mg/m2/4 litres of perfusion liquid (dextrose 1.5%). Single intraoperative dose.
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.
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
Eligibility Criteria
You may qualify if:
- Patients of both sexes, aged ≥18 years and ≤75 years (patients between 70-75 years old will be discussed in committee).
- Adenocarcinoma of the colon, sigmoid colon and rectum-sigmoid junction that is cT4a/b according to the American Joint Committee on Cancer (AJCC) TNM eight edition. Pre-treatment diagnosis by imaging test (CT scan or MRI). High-risk cT3 with invasion into surrounding fat greater than 5mm may be included.
- Nodal extension: cN0, the presence of cN1/2 according to AJCC TNM 8th edition is allowed as long as they can be resected. Pre-treatment diagnosis by imaging test (CT scan or MRI).
- Metastatic extension: cM0. Patients with cM1 are not allowed to be included.
- ECOG 0-1.
- Microsatellite stability (pMMR).
- Informed consent duty completed.
You may not qualify if:
- Presence of metastases (M1). If liver or peritoneal metastases are present at the time of surgery, the patient will be excluded from the study and treated according to the new stage.
- Presence of un-resectability criteria in the pretreatment work-up, un-resectability will be discussed in MDT with expert oncologic surgeons.
- Presence of microsatellite instability (dMMR).
- Presence of deficit of DPD.
- Urgent intervention due to obstruction or perforation if the primary tumour is removed. Bridge interventions such as transit shunts without removal of the primary tumour or percutaneous drainage of collections prior to neoadjuvant treatment or scheduled surgery will be accepted.
- Extraperitoneal rectal cancer (medium-low) (avoiding alterations due to neoadjuvant radiotherapy).
- Coexistence of another relevant malignant neoplastic disease (synchronous colon and rectum-sigmoid tumours are accepted as long as the stage is equal or lower than the treated tumour), it will be discussed in steering committee.
- Severely impaired hepatic, renal or cardiovascular function.
- Intolerance to treatment.
- Gestational or lactating women.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Hospital Universitario Reina Sofia
Córdoba, Córdoba, 14004, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Alvaro Arjona Sánchez, MD., Ph.D.
MAIMONIDES BIOMEDICAL RESEARCH INSTITUTE
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 8, 2025
First Posted
January 20, 2025
Study Start
December 31, 2025
Primary Completion (Estimated)
June 1, 2030
Study Completion (Estimated)
December 31, 2030
Last Updated
November 24, 2025
Record last verified: 2025-11