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

Conditions
Liver Metastasis Colon Cancer
Interventions
Device: TACE+ systemic Bevacizumab
Drug: FOLFIRI+Bevacizumab
Device: TACE
Registration Number
NCT03732235
Lead Sponsor
Giammaria Fiorentini
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

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
50
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
TACE+ systemic BevacizumabTACE+ systemic BevacizumabTACE 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.
FOLFIRI+BevacizumabFOLFIRI+BevacizumabFOLFIRI 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.
TACETACETACE 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.
Primary Outcome Measures
NameTimeMethod
time to progression1 year

time from first treatment to progression will be computed

Secondary Outcome Measures
NameTimeMethod
Tumor response3 months

CT scan will be performed to assess tomuor response

Number of adverse events3 motnhs

Number of adverse events will be monitored

Trial Locations

Locations (1)

Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore

🇮🇹

Pesaro, PU, Italy

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