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

NCT ID: NCT03732235

Last Updated: 2019-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-10-01
• Study Completion Date: 2021-12-31

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

Conditions

Liver Metastasis Colon Cancer

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

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.

TACE+ systemic Bevacizumab

Intervention Type: DEVICE

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.

FOLFIRI+Bevacizumab

Intervention Type: DRUG

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.

TACE

Intervention Type: DEVICE

PEG embolics

Interventions

TACE+ systemic Bevacizumab

PEG embolics

Intervention Type: DEVICE

FOLFIRI+Bevacizumab

antiangiogenic factor

Intervention Type: DRUG

TACE

PEG embolics

Intervention Type: DEVICE

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Giammaria Fiorentini

OTHER

Sponsor Role: lead

Responsible Party

Giammaria Fiorentini

Dr.

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore

Pesaro, PU, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Giammaria Fiorentini, MD

Role: CONTACT

g.fiorentini@alice.it

+390721364005

Donatella Sarti, PhD

Role: CONTACT

d.sarti@fastwebnet.it

+390721364018

Facility Contacts

Giammaria Fiorentini, MD

Role: primary

giammaria.fiorentini@ospedalimarchenord.it

+390721364124

References

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.

Reference Type: DERIVED

PMID: 32111770 (View on PubMed)

Other Identifiers

EMBOBEVA

Identifier Type: -

Identifier Source: org_study_id