Local Immunomodulation After Radiofrequency of Unresectable Colorectal Liver Metastases

NCT04062721 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 19RME-LICORN
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective of this trial is to determine feasibility and tolerance of the human body to RFA associated with local immunomodulation carried out using a thermoreversible hydrogel combined with 2 immunomodulators, GMCSF and Mifamurtide. The main endpoint of the study is the feasibility, the frequency and the nature of per and post-operative adverse events of the in situ injection of an immunomodulatory hydrogel after radiofrequency of unresectable colorectal liver metastases. The secondary objective is one-year progression free survival rate.

Conditions

Unresectable Colorectal Liver Metastases

Keywords

Colorectal cancer; Liver metastases; Radiofrequency; Immunomodulation

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events

  All grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 including post-operative and immune-related complications within 3 months after surgery.

  at 3 months

Secondary Outcomes (5)

• Progression free survivor (PFS) rate at 12 months

  at 12 months

• Median PFS

  at 12 months

• Median overall survival (OS)

  at 24 month

• Response rate

  at 12 months and 24 months

• Potential predictive biomarkers

  at baseline and every two months until 24 months

Study Arms (1)

Chemotherapy + RFA + in situ immunotherapy

EXPERIMENTAL

Patients with non-resectable CRC liver-only metastases.

Drug: Chemotherapy; Procedure: Radiofrequency ablation (RFA); Drug: In situ immunotherapy

Interventions

Chemotherapy DRUG

Chemotherapy (at the investigator's choice) for ≥ 2 months before RFA (with controlled disease) and resumed 4-6 weeks after RFA to achieve 6-month total duration.

Chemotherapy + RFA + in situ immunotherapy

Radiofrequency ablation (RFA) PROCEDURE

Complete macroscopic ablation by RFA.

Chemotherapy + RFA + in situ immunotherapy

In situ immunotherapy DRUG

Hydrogel combining TLR or NOD2 agonist and GM-CSF will be injected in 1, 2 or 3 distinct lesions after RFA.

Chemotherapy + RFA + in situ immunotherapy

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations;
• Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up;
• Histologically or cytologically proven CRC;
• Non-resectable liver metastases from CRC without detectable extra-hepatic disease, on abdomino-pelvic computed tomography (CT) or magnetic resonance imaging (MRI) and chest CT by the consulting hepatobiliary surgeon and radiologist. Unresectability is defined as no possibility to completely resect all tumor lesions;
• Age ≥ 18 years;
• ECOG PS 0-1;
• Controlled disease (stability or objective response) with chemotherapy (≥ 2 months) for liver metastases;
• Liver metastases ≥ 3 and \<10, including ≥ 3 lesions accessible to RFA;
• Maximum diameter of 4 cm for lesions to be treated by RFA;
• Metastatic involvement of the liver ≤50%;
• Complete treatment of all liver lesions judged possible, either by RFA alone or by combination with resection of resectable lesions and RFA of the remaining non-resectable liver deposits;
• Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan \< 4 weeks);
• Adequate organ function, as defined by the following:
• Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN);
• Total serum bilirubin \< 1.5 ULN;

You may not qualify if:

• Any other malignancy in the past 10 years (except carcinoma of the cervix in situ or no melanoma skin cancer);
• Clinical significant cardiovascular disease;
• Uncontrolled hypertension, bleeding disorders or coagulopathy, active infection;
• Major surgical procedures within 28 days before RFA;
• Concurrent enrolment in another clinical study, unless it is an observational (noninterventional) or supportive care clinical study or during the follow-up period of an interventional study;
• Receipt of the last dose of anticancer therapy (investigational product, chemotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 21 days prior to the RFA. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics properties of an agent, a longer wash-out period will be required;
• Histology other than adenocarcinoma;
• Extensive tumor massively replacing both entire lobes;
• Obstructive jaundice (bilirubin \> 1.5 ULN) without adequate biliary drainage;
• History of allogenic organ transplantation;
• Any systemic steroid therapy whatever the duration of this corticotherapy;
• Note: The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication);
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies); Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen \[HBc\] antibody test) are eligible.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Digestive Surgery Department, Ambroise Pare University Hospital, APHP

Boulogne-Billancourt, 92100, France

Location

Related Publications (2)

• Lemdani K, Seguin J, Lesieur C, Al Sabbagh C, Doan BT, Richard C, Capron C, Malafosse R, Boudy V, Mignet N. Mucoadhesive thermosensitive hydrogel for the intra-tumoral delivery of immunomodulatory agents, in vivo evidence of adhesion by means of non-invasive imaging techniques. Int J Pharm. 2019 Aug 15;567:118421. doi: 10.1016/j.ijpharm.2019.06.012. Epub 2019 Jun 6.

  PMID: 31176849 BACKGROUND

• Lemdani K, Mignet N, Boudy V, Seguin J, Oujagir E, Bawa O, Peschaud F, Emile JF, Capron C, Malafosse R. Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma. Oncoimmunology. 2019 Jan 10;8(3):1550342. doi: 10.1080/2162402X.2018.1550342. eCollection 2019.

  PMID: 30723580 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Drug Therapy; Radiofrequency Ablation

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

Intervention Hierarchy (Ancestors)

Therapeutics; Radiofrequency Therapy; Ablation Techniques; Surgical Procedures, Operative

Study Officials

• Robert Malafosse, MD

  Digestive Surgery Department, Ambroise Pare University Hospital, Boulogne-Billancourt, France

  PRINCIPAL INVESTIGATOR

• Cindy NEUZILLET, MD, PhD

  Digestive Surgery Department, Ambroise Pare University Hospital, Boulogne-Billancourt, France

  STUDY DIRECTOR

Central Study Contacts

Robert Malafosse, MD

CONTACT

+ 33 1 49 09 47 82; robert.malafosse@aphp.fr

Cindy NEUZILLET, MD, PhD

CONTACT

+ 33 1 49 09 55 86; cindy.neuzillet@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: August 20, 2019
• Study Start: August 1, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)