Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease

Last updated: April 9, 2024
Sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
Overall Status: Active - Recruiting

Phase

2

Condition

Neoplasm Metastasis

Treatment

LIVERPEARLS-Irinotecan

FOLFOX regimen

Anti-EGFR or Bevacizumab

Clinical Study ID

NCT04595266
GEMCAD-1802
2020-003795-40
  • Ages > 18
  • All Genders

Study Summary

Non-commercial, prospective, randomized, multicenter, national, phase II, open-label comparative clinical trial.

The patients will be randomized in a 1: 1 ratio in two arms:

Control arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab Experimental arm. Systemic chemotherapy with FOLFOX6m + monoclonal Ab + Intra-arterial liver chemotherapy with LIFEPEARLS-IRINOTECAN (catheterization and infusion of 100 +/- 50 micron microspheres loaded with 100 mg of irinotecan in both liver lobes) cycles 2 and 4.

The main objective is to evaluate the radiological objective response rate according to the RECIST version 1.1 criteria at 6 months. Secondary objectives include: Evaluate overall survival, progression-free survival (PFS), safety profile, hepatic PFS, R0 liver surgery rate.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Patients aged ≥ 18 years.
  • Patients with colorectal cancer and exclusive liver metastases with poor prognosticcriteria,> 3 lesions and / or size> 5 cm. Patients with a diagnosis of livermetastases with synchronous presentation or with a disease-free interval may beincluded. If the primary tumor has not been resected, it must be clinically stable.
  • Measurable disease following RECIST version 1.1 criteria
  • Adequate bone marrow function, according to:
  1. Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl can be transfusedbefore inclusion in the study
  2. Platelet count ≥ 100 x 109 / L
  3. Absolute Neutrophil Count (ANC) ≥ 1.5x 109 / L
  • Adequate liver function, according to:
  1. Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN)
  2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
  3. Alkaline phosphatase ≤ 5 x ULN or ≤10 x ULN in the presence of bone metastases
  4. Adequate renal function, with creatinine levels <1.5 mg / dL. Blood UreicNitrogen (BUN)> 50 ml / min.
  5. Albumin> 3.0 g / dL
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Patients capable of understanding the information and giving their written informedconsent to participate in the study
  • Women of childbearing potential must commit to sexual abstinence or use of barriercontraceptive methods during the study and must have a negative pregnancy test.

Exclusion

Exclusion Criteria:

  • Extension of the disease> 50% of the liver parenchyma (evaluated by CT performedwithin the month prior to inclusion)
  • Previous chemotherapy treatment for metastatic colorectal cancer
  • Clinically significant cardiovascular diseases: cerebrovascular accident / stroke (≤ 6months before inclusion in the trial), myocardial infarction (≤ 6 months beforeinclusion in the trial), unstable angina, uncontrolled hypertension, congestive heartfailure of New York Heart Association (NYHA) grade II or higher or severe cardiacarrhythmia.
  • History of malignancy in the last three years, except for basal cell carcinoma of theskin or carcinoma in situ of the cervix treated appropriately.
  • Altered coagulation (Quick> 50%)
  • Patients with active infectious processes
  • Patients with any of the contraindications specified in the technical data sheet ofthe study drug or with allergies to some of the drugs used
  • Pregnant or lactating patients
  • Portal thrombosis
  • Severe portal hypertension
  • Extrahepatic metastases

Study Design

Total Participants: 48
Treatment Group(s): 3
Primary Treatment: LIVERPEARLS-Irinotecan
Phase: 2
Study Start date:
June 29, 2021
Estimated Completion Date:
January 31, 2025

Study Description

Hepatic intra-arterial therapy (TACE) with irinotecan has been used in several prospective studies demonstrating an acceptable toxicity profile. Two randomized phase II studies have evaluated the efficacy of TACE with irinotecan compared to conventional chemotherapy in metastatic colon cancer. A second-line treatment study demonstrated an increase in PFS in the TACE versus FOLFIRI treatment arm.

A prospective open, randomized, multicenter phase II study is proposed that will include patients with liver metastases of colorectal origin with poor prognostic criteria.

LIFEPEARLS® is a CE marked medical device consisting of microspheres for use in chemoembolization. The device uses 100 +/- 50 micron microspheres of hydrogel into which chemotherapeutic agents are loaded and delivered into the hepatic artery to treat liver tumors. This device allows the continuous release of irinotecan in liver tumors causing a specific necrosis. The penetration of irinotecan into the tumor tissue is deeper thanks to the microspheres, avoiding proximal occlusion of the vessels supplying the tumor.

Systemic treatment will be administered according to the usual guidelines:

-FOLFOX6m for 6 months + monoclonal Ab (cycles are repeated every 15 days) Premedication: Dexamethasone 20 mg IV + ondansetron 8mg IV

The dose of FOLFOX will be:

Leucovorin: 400 mg / m2 IV over 15 minutes on day 1 of each cycle. Fluorouracil (5-FU): 400mg / m2 IV bolus (15 min) followed by continuous IV infusion for 46 h of 2,400 mg / m2 on day 1 of each cycle.

Oxaliplatin 85 mg / m2 IV over 120 minutes on cycle day 1. In case of RAS wt colorectal cancer administer anti-EGFR together with FOLFOX6m, and in case of mutated RAS colorectal cancer administer Bevacizumab together with FOLFOX6m.

In the combination arm of systemic chemotherapy with IRINOPEARL, in the 2nd and 4th cycles, chemotherapy will be replaced by treatment with hepatic chemoembolization with IRINOPEARL.

The disease will be evaluated by CT or MRI at baseline and every 12 weeks until progression according to RECIST 1.1 criteria.

Connect with a study center

  • Hospital Parc Taulí

    Sabadell, Barcelona
    Spain

    Active - Recruiting

  • Hospital Universitario de Alicante

    Alicante,
    Spain

    Site Not Available

  • Hospital Clínic

    Barcelona,
    Spain

    Active - Recruiting

  • Hospital de la Santa Creu i Sant Pau

    Barcelona,
    Spain

    Active - Recruiting

  • H. Univ. Ramón y Cajal

    Madrid, 28044
    Spain

    Site Not Available

  • Hospital Universitario 12 de Octubre

    Madrid,
    Spain

    Active - Recruiting

  • Hospital Universitario La Paz

    Madrid,
    Spain

    Site Not Available

  • Complejo Hospitalario de Navarra

    Pamplona,
    Spain

    Active - Recruiting

  • Hospital Universitario de Canarias

    Tenerife,
    Spain

    Site Not Available

  • Hospital Universitari i Politècnic La Fe

    Valencia, 46026
    Spain

    Active - Recruiting

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