Liver-directed chemotherapy after surgery of liver metastases of colorectal cancer in patients with high risk of recurrence of their disease.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-05

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Fondation ARCAD

External identifiers

EU CT number

2025-523913-27-00

ClinicalTrials.gov

NCT07284394

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the trial is to evaluate the efficacy of postoperative HAI of oxaliplatin plus
IV chemotherapy after curative-intent resection of CRLM in patients at high risk in terms of PFS.

Secondary objectives 8

1. Evaluation of efficacy in term of OS between treatment arms
2. Evaluation of efficacy in term of hepatic RFS between treatment arms
3. Evaluation of efficacy in term of pattern of recurrence or progression between treatment arms
4. Evaluation of feasibility of HAI of oxaliplatin by selective angiography
5. Evaluation of toxicity of postoperative HAI and IV chemotherapy, in particular HAI catheter related complications and peripheral sensory neuropathy
6. Description of the type of treatments used in case of recurrence
7. Evaluation of tumor response following reintroduction of chemotherapy in case of recurrence
8. Evaluation of patients’ quality of life

Conditions and MedDRA coding

Participants with R0/R1 resected liver metastases from colorectal cancer (CRLM).

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, an impartial witness of their choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent
2. Age ≥ 18 years
3. ECOG performance status 0-1
4. Histologically confirmed stage IV pMMR CRC
5. Resected CRLM by one- or two-stage procedures including reverse strategy
6. Partial Response or Stability Disease (RECIST v1.1) to preoperative cytotoxic doublet or triplet IV chemotherapy +/- targeted agent before surgery
7. Curative-intent (R0/R1 resection ± local ablation) surgery of 4 or more CRLM
8. No macroscopic residual (hepatic or extra-hepatic) disease on postoperative CT scan within 4 weeks after surgery confirmed during local multidisciplinary tumor board (except up to 3 lung nodules < 10 mm deemed amenable to curative-intent resection/local ablation and non-resected primary tumor with no or mild symptoms)
9. Eligible to HAI of oxaliplatin by (permanent or selective) catheterization defined as the absence of medical (any contraindication to oxaliplatin administration, mainly residual peripheral sensory neuropathy grade < 2) and technical (vascular anatomy to perform HAI chemotherapy) contraindications to administer oxaliplatin-based doublet or triplet chemotherapy within 8 weeks from surgery during at least 4 cycles evaluated by interventional radiologist and medical oncologist
10. Adequate organ and marrow function as indicated by the following laboratory values: bilirubin < 1.5 x upper limit of normal values (ULN), aminotransferases < 5 ULN, alkaline phosphatase < 5 ULN, International normalized ratio (INR) < 1.5 ULN, platelets > 100,000/mm3, neutrophils>1500/mm3
11. Women of childbearing potential must have a negative pregnancy test done within 30 days before randomisation and 72 hours prior treatment initiation
12. Patients must agree to use adequate contraception methods for the duration of study treatment and : a. women of childbearing potential (WOCBP) must use highly effective contraception at least: - 15 months after the end of the treatment with oxaliplatin, - 6 months after the end of the treatment with fluorouracile and iri notecan b. men must use contraception at least: - 12 months after the end of the treatment with oxaliplatin, 3 months after the end of the treatment with fluorouracile and irinotecan.
13. Patients must be willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests and other study procedures
14. Patients must be affiliated to a Social Security System (or equivalent)

Exclusion criteria 15

1. Stage IV dMMR CRC
2. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
3. Persons deprived of their liberty or under protective custody or guardianship
4. Incomplete (R2) surgery or residual (hepatic or extrahepatic) disease on postoperative CT scan within 4 weeks after surgery or symptomatic primary tumours in case of reverse strategy
5. Previous history of colorectal liver metastases treated with curative intent
6. Patients with contraindications for HAI or IV doublet or triplet administration as limiting anatomical variations of hepatic artery, peripheral sensory neuropathy ≥ grade 2 (NCICTAE v.5.0), gastric/duodenal ulcer or significant chronic liver disease (resulting in portal hypertension and/or liver failure)
7. Patient with a dihydropyrimidine dehydrogenase deficiency (DPD)
8. Ionic disorders as: a. Potassium < 3,5 mEq/L (< 3,5 mmol/L) b. Magnesium < 1,8 mg/dL (< 0,70 mmol/L) c. Total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L)
9. Medical history of other concomitant or previous malignant disease, except adequately treated in situ carcinoma of the uterine cervix, basal or squamous cell carcinoma of the skin, or cancer in complete remission for ≥5 years
10. Pregnant women or women who are breast-feeding
11. Participation in another therapeutic trial within the 30 days prior to randomisation
12. QT/QTc interval longer than 450 msec for men and longer than 470 msec for women
13. Persistent toxicities related to prior treatment of grade > 1
14. Known history of hypersensitivity to trial treatments or any of their excipients or : o for 5-fluorouracil in case of: potentially serious infection, patients with poor nutritional status, recent or concomitant treatment with brivudine, live attenuated vaccines, clinically significant active heart disease or myocardial infarction within 6 months o for oxaliplatin in case of severely impaired renal function (creatinine clearance less than 30 ml/min) o for irinotecan in case of: chronic inflammatory bowel disease and/or bowel obstruction, concomitant use with St John's Wort, live attenuated vaccines
15. Patients who already received 6 months of FOLFOX or 3 months of CAPOX as adjuvant therapy following resection of the primary tumor completed less than 6 months ago

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the progression-free survival (PFS), defined as the time between randomization and the occurrence of the first oncological event observed according to RECIST v1.1 criteria, such as local or metastatic recurrence, progression or death from any cause.

Secondary endpoints 8

1. Overall survival (OS), defined as the time from randomization to death, irrespective of cause. Patients still alive at the time of the analysis will be censored at the date of last follow-up.
2. Hepatic recurrence-free survival (h-RFS), defined as the time from randomization to the occurrence of the first hepatic relapse according to RECIST v1.1 criteria or death from any cause. Patients alive without hepatic recurrence at the time of the analysis will be censored at the date of last follow-up.
3. Patterns of progression or recurrence, defined as hepatic recurrence rate and extra hepatic recurrence or progression rate as first oncological event.
4. Feasibility, defined as: - Proportion of patients receiving at least 4 cycles of oxaliplatin arm. - Relative dose-intensity of oxaliplatin (calculated over the first three months of treatment).
5. Safety assessed according to Common Terminology Criteria for Adverse Events (CTCAE v5.0) system for treatment toxicity. In HAI arm catheter-related complications and treatment procedures will be analyzed. AE will be coded with the MedDRA dictionary.
6. Type of chemotherapy (IV, HAI, lines and cycles) and rate of curative intent treatments (surgery, local ablation or radiotherapy) in case of recurrence
7. Tumor response rate according to RECIST v1.1 criteria following reintroduction of chemotherapy in case of recurrence
8. Health-related Quality of life evaluated with European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ) EORTC QLQ-C30 associated with the Liver colorectal metastasis Module QLQ-LMC21

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine AIT RAHMOUNE

Locations

1 EU/EEA country · 17 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 14 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications