TACE Associated to Systemic Bevacizumab for the Treatment of Refractory Liver Metastases From Colorectal Cancer
Keywords
Abstract
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
Dates
| Last Verified: | 01/31/2019 |
| First Submitted: | 10/29/2018 |
| Estimated Enrollment Submitted: | 11/04/2018 |
| First Posted: | 11/05/2018 |
| Last Update Submitted: | 02/18/2019 |
| Last Update Posted: | 02/20/2019 |
| Actual Study Start Date: | 09/30/2018 |
| Estimated Primary Completion Date: | 09/30/2021 |
| Estimated Study Completion Date: | 11/30/2021 |
Condition or disease
Intervention/treatment
Device: TACE+ systemic Bevacizumab
Drug: FOLFIRI+Bevacizumab
Device: TACE
Phase
Arm Groups
| Arm | 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 |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Sampling method | Non-Probability Sample |
| Accepts Healthy Volunteers | Yes |
| 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). |
Outcome
Primary Outcome Measures
1. time to progression [1 year]
Secondary Outcome Measures
1. Tumor response [3 months]
2. Number of adverse events [3 motnhs]
