TACE Associated to Systemic Bevacizumab for the Treatment of Refractory Liver Metastases From Colorectal Cancer (EMBOBEVA)

Observational Study on Transarterial Chemoembolization With Irinotecan-loaded Embolics Associated With Systemic Bevacizumab for the Treatment of Refractory Liver Metastases From Colorectal Cancer

Transarterial chemoembolization (TACE) is an effective, minimally invasive therapy that is widely used for unresectable colorectal cancer liver metastases (CRC-LM) treatment. Chemoembolization, however, induces a hypoxic micro-environment, which increases neo-angiogenesis, and may promote early progression. For this reason, efficacy may be improved by associating TACE with an angiogenesis inhibitor, such as bevacizumab.

The use of FOLFIRI associate to Bevacizumab is part of clinical practice and is commonly used for the therapy of patients with CRC-LM both wild type and mutant.

This case-control observational study aim to compare patients treated with TACE using Irinotecan-loaded embolics followed by systemic Bevacizumab versus patients treated with FILFIRI+ Bevacizumab

Study Overview

• Status: Unknown
• Conditions: Liver Metastasis Colon Cancer
• Intervention / Treatment: Device: TACE+ systemic Bevacizumab; Drug: FOLFIRI+Bevacizumab; Device: TACE

Detailed Description

TACE is indicated for the treatment of unresectable CRC_LM, patients who are refractory to systemic chemotherapy, elderly, or have a poor performance status, and is usually performed using irinotecan (IRI) covalently loaded onto embolics.

Although chemoembolization with irinotecan-loaded embolics results in an objective response, this method creates a hypoxic micro-environment. Hypoxia induces and activates the HIF-1 and HIF 2 hypoxia-inducible transcription factors, which promote high-level VEGF expression and subsequent neo-angiogenesis.

This may provide a mechanism for early relapse and progression following TACE and strongly support a rational for following TACE therapy with a therapeutic inhibitor of angiogenesis, such as bevacizumab.

The use of FOLFIRI associate to Bevacizumab is part of clinical practice and is commonly used for the therapy of patients with CRC-LM both wild type and mutant.

This case-control observational study aim to compare patients treated with TACE using Irinotecan-loaded embolics followed by systemic Bevacizumab versus patients treated with FILFIRI+ Bevacizumab

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• Italy
  • PU
    • Pesaro, PU, Italy, 61122
      • Recruiting
      • Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
      • Contact: Giammaria Fiorentini, MD; Phone Number: +390721364124; Email: giammaria.fiorentini@ospedalimarchenord.it
      • Principal Investigator: Giammaria Fiorentini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This was a prospective observational single center study.that involved CRC-LM patients treated with TACE, using irinotecan-loaded PEG embolics (LIFIRI), followed by the intravenous administration of bevacizumab. This group was compared to CRC-LM patients treated with FOLFIRI+Bevacizumab.

CRC-LM patients were instructed by physician about the study procedures and after signing informed consent choose the type of theratment TACE+bevacizumab or FOLOFIRI+bevacizumab

Description

Inclusion Criteria:

• Written informed consent
• >18 years old;
• diagnosed with unresectable CRC-LM (for reasons of anatomy, co-morbidity, patient's wishes, lack of response to standard therapy with intravenous or oral fluoropyrimidine, oxaliplatin, irinotecan or biological agents (bevacizumab, cetuximab, panitumumab);
• Eastern Cooperative Oncology Group (ECOG) 0-1;
• measurable tumor size by mRECIST [6];
• ≤40% liver involvement;
• a life expectancy of at least 3 months,
• blood biochemistry within the normal range.

Exclusion Criteria:

• contraindication for angiographic catheterization;
• extensive extra-hepatic disease;
• pregnancy or breast-feeding,
• other severe clinical contraindications (e.g. liver failure, ascites, cardiovascular diseases and/or chronic obstructive pulmonary disease).

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TACE+ systemic Bevacizumab; TACE was performed, using 2 ml of LifePearl® with 100 micron diameter (Terumo Europe NV, Leuven, Belgium) loaded with Irinotecan (100 mg), diluted in 5 ml of non-ionic contrast solution and 5 ml of distilled water, infused at fixed speed of 1ml/minute for a median time of 12 minutes (range 8-16 minutes). A second TACE was performed after 30 days if needed according to physician choice. Bevacizumab (5 mg/kg) therapy was initiated 15 days after first round of TACE and was repeated every two weeks, for a total of 8 cycles.	Device: TACE+ systemic Bevacizumab; PEG embolics
FOLFIRI+Bevacizumab; FOLFIRI consists of 5-FU administered as a 48-hour continuous infusion to a total dose of 3,200 mg/m2 without a bolus, leucovorin 200 mg/m2, irinotecan 165 mg/m2 Bevacizumab (5 mg/kg) therapy was repeated every two weeks, for a total of 8 cycles.	Drug: FOLFIRI+Bevacizumab; antiangiogenic factor
TACE; TACE was performed, using 2 ml of LifePearl® with 100 micron diameter (Terumo Europe NV, Leuven, Belgium) loaded with Irinotecan (100 mg), diluted in 5 ml of non-ionic contrast solution and 5 ml of distilled water, infused at fixed speed of 1ml/minute for a median time of 12 minutes (range 8-16 minutes). A second TACE was performed after 30 days if needed according to physician choice.	Device: TACE; PEG embolics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
time to progression	time from first treatment to progression will be computed	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor response	CT scan will be performed to assess tomuor response	3 months
Number of adverse events	Number of adverse events will be monitored	3 motnhs

Collaborators and Investigators

• Sponsor: Giammaria Fiorentini

Publications and helpful links

General Publications

• Fiorentini G, Sarti D, Nardella M, Inchingolo R, Nestola M, Rebonato A, Guadagni S. Chemoembolization Alone or Associated With Bevacizumab for Therapy of Colorectal Cancer Metastases: Preliminary Results of a Randomized Study. In Vivo. 2020 Mar-Apr;34(2):683-686. doi: 10.21873/invivo.11824.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: November 5, 2018
• First Posted (Actual): November 6, 2018

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: February 19, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Bevacizumab; Irinotecan; Liver Metastases; Anti-angiogenesis; FOLFIRI; Transarterial chemoembolization; Embolics
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Estrogens, Non-Steroidal; Estrogens; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Chlorotrianisene; Bevacizumab
• Other Study ID Numbers: EMBOBEVA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study protocol will be shared
• IPD Sharing Time Frame: 1 year
• IPD Sharing Access Criteria: request by email to Principal Investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No