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

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ClinicalTrials.gov Identifier: NCT03732235

Recruitment Status : Unknown

Verified February 2019 by Giammaria Fiorentini, International Group of Endovascular Oncology.
Recruitment status was: Recruiting

First Posted : November 6, 2018

Last Update Posted : February 21, 2019

Sponsor:

Information provided by (Responsible Party):

Giammaria Fiorentini, International Group of Endovascular Oncology

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment
Liver Metastasis Colon Cancer	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 Design

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Study Type :	Observational
Estimated Enrollment :	50 participants
Observational Model:	Case-Control
Time Perspective:	Prospective
Official Title:	Observational Study on Transarterial Chemoembolization With Irinotecan-loaded Embolics Associated With Systemic Bevacizumab for the Treatment of Refractory Liver Metastases From Colorectal Cancer
Actual Study Start Date :	October 1, 2018
Estimated Primary Completion Date :	October 2021
Estimated Study Completion Date :	December 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Bevacizumab

U.S. FDA Resources

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures :

time to progression [ Time Frame: 1 year ]
time from first treatment to progression will be computed

Secondary Outcome Measures :

Tumor response [ Time Frame: 3 months ]
CT scan will be performed to assess tomuor response
Number of adverse events [ Time Frame: 3 motnhs ]
Number of adverse events will be monitored

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
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

Criteria

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).

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03732235

Contacts

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Contact: Giammaria Fiorentini, MD	+390721364005	g.fiorentini@alice.it
Contact: Donatella Sarti, PhD	+390721364018	d.sarti@fastwebnet.it

Locations

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

Sponsors and Collaborators

Giammaria Fiorentini

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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Responsible Party:	Giammaria Fiorentini, Dr., International Group of Endovascular Oncology
ClinicalTrials.gov Identifier:	NCT03732235
Other Study ID Numbers:	EMBOBEVA
First Posted:	November 6, 2018 Key Record Dates
Last Update Posted:	February 21, 2019
Last Verified:	February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Study protocol will be shared
Supporting Materials:	Study Protocol
Time Frame:	1 year
Access Criteria:	request by email to Principal Investigator

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Giammaria Fiorentini, International Group of Endovascular Oncology:


Liver Metastases Transarterial chemoembolization Bevacizumab Anti-angiogenesis	Irinotecan Embolics FOLFIRI

Additional relevant MeSH terms:

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Neoplasm Metastasis Neoplasms, Second Primary Liver Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Neoplastic Processes Pathologic Processes Liver Diseases Bevacizumab Chlorotrianisene	Antineoplastic Agents, Immunological Antineoplastic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Estrogens, Non-Steroidal Estrogens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal

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