COLDFIRE-III Trial: Efficacy of Irreversible Electroporation and Stereotactic Body Radiotherapy for Perivascular and Peribiliary Colorectal Liver Metastases

NCT06185556 | Recruiting Phase 2

• 1 other identifier: NL83557.018.23
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this phase IIb/III, prospective, randomized clinical trial is to compare the efficacy of irreversible electroporation (IRE) with stereotactic body radiotherapy (SBRT) in patients with perivascular or peribiliary colorectal liver metastases (CRLM), that are not amenable for surgical resection or thermal ablation. Efficacy is assessed in terms of local control at 2 years.

Conditions

Colorectal Cancer; Liver Metastases; Liver Metastasis Colon Cancer; Unresectable Solid Tumor

Keywords

Colorectal liver metastases; colorectal hepatic metastases

Outcome Measures

Primary Outcomes (1)

• Local control

  Local control is defined as no objectified signs for local tumor progression on imaging acquired 23-24 months following start of the initial study procedure, according to the RECIST criteria. Site recurrences within the first 12 months that are successfully retreated once using the same technique (re-IRE or re-SBRT), thermal ablation or surgical resection will not be regarded as an event for local control. Per patient analysis.

  2 years

Secondary Outcomes (10)

• Overall survival (OS) per patient

  Assessed up to 5 years

• Local tumor progression-free survival (LTPFS) per patient and per tumor.

  Assessed up to 5 years

• Distant tumor progression-free survival (DPFS) per patient

  Assessed up to 5 years

• Time to progression (TTP) per patient

  Assessed up to 5 years

• Safety per procedure and per patient

  Assessed up to 5 years

Study Arms (2)

A: Irreversible electroporation

ACTIVE COMPARATOR

Irreversible electroporation (IRE) is a primarily non-thermal, local ablative technique that utilizes electrical pulses to destroy tumor tissue. Theoretically, IRE only affects viable tumor tissue, leaving surrounding vital structures relatively intact. It is therefore considered to cause less morbidity than thermal ablative strategies.

Procedure: Irreversible electroporation

B: Stereotactic body radiotherapy

ACTIVE COMPARATOR

Stereotactic body radiotherapy (SBRT) is a form of external beam radiation that has important advantages over conventional radiotherapy such as a more precise and greater biological dose delivery and hence less toxicity and presumably better outcome.

Radiation: Stereotactic body radiotherapy

Interventions

Irreversible electroporation PROCEDURE

Percutaneous (CT-guided) irreversible electroporation of 1-3 perivascular and peribiliary colorectal liver metastasis.

A: Irreversible electroporation

Stereotactic body radiotherapy RADIATION

Stereotactic body radiotherapy (CT- or MRI-guided) of 1-3 perivascular and peribiliary colorectal liver metastases.

B: Stereotactic body radiotherapy

Eligibility Criteria

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

You may qualify if:

• Histological documentation of primary colorectal tumor is available;
• CRLM visible on ceCT and/or MRI, size 0-5 cm and not eligible for resection or thermal ablation due to location close to a vessel or bile duct;
• Additional CRLM are allowed if considered either resectable or ablatable with a maximum of 10 CRLM. In patients with extrahepatic disease, a maximum of 5 additional CRLM is allowed;

You may not qualify if:

• Prior focal liver treatment is allowed;
• Subjects should preferably be treated with neo-adjuvant systemic therapy;
• Subjects with recurrent (either local or distant-hepatic) CRLM after previous focal treatment who are unsuitable for (further) systemic therapy (further downsizing or conversion to resectable disease improbable);
• ASA classification 0 - 3;
• Age \>18 years;
• Written informed consent;
• Radical treatment unfeasible or unsafe (e.g. insufficient FLR);
• \>10 CRLM; \>5 CRLM when extra-hepatic disease is present;
• Positive para-aortal lymph nodes, celiac lymph nodes, adrenal metastases, pleural carcinomatosis or peritoneal carcinomatosis;
• Subjects who have progressive disease after neo-adjuvant systemic therapy;
• History of epilepsy;
• History of cardiac disease:
• Uncontrolled hypertension. Blood pressure must be ≤160/95 mmHg at the time of screening on a stable antihypertensive regimen;
• Compromised liver function (e.g. signs of portal hypertension, INR \> 1,5 without use of anticoagulants, ascites);
• Pregnant or breast-feeding subjects;

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• Angiodynamics, Inc.: collaborator

Study Sites (1)

Amsterdam UMC - location VUmc

Amsterdam, North Holland, 1081 HV, Netherlands

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Electroporation; Radiosurgery

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)

Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Electrochemical Techniques; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• Martijn R. Meijerink, Prof.

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle J. Vos, M.D.

CONTACT

+3120-4444571; interventieradiologie@vumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: A prospective, randomized clinical trial.

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: December 29, 2023
• Study Start: August 20, 2024
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 23, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)