Clinical trial NCT03732235: TACE Associated to Systemic Bevacizumab for the Treatment of Refractory Liver Metastases From Colorectal Cancer
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Liver Metastasis Colon Cancer
Keywords: Liver Metastases
Transarterial chemoembolization
Bevacizumab
Anti-angiogenesis
Irinotecan
Embolics
FOLFIRI
Lead sponsor: International Group of Endovascular Oncology
Sponsor class: OTHER
First posted: 2018-11-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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

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

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

Eligibility 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).

Primary outcomes:
measure: time to progression
timeFrame: 1 year
Secondary outcomes:
measure: Tumor response
timeFrame: 3 months
measure: Number of adverse events
timeFrame: 3 motnhs
Other outcomes:
Locations:
city: Pesaro
country: Italy
facility: Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
state: PU
Study officials:
References:
citation: 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.