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

Primary Purpose

Colorectal Cancer Metastatic, Liver Metastasis Colon Cancer

Status
Recruiting
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
FOLFOX regimen
Anti-EGFR or Bevacizumab
LIVERPEARLS-Irinotecan
Sponsored by
Grupo Espanol Multidisciplinario del Cancer Digestivo
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colorectal Cancer Metastatic focused on measuring Colorectal cancer, Chemoembolization, LIVERPEARLS-Irinotecan, Liver metastasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged ≥ 18 years.
  • Patients with colorectal cancer and exclusive liver metastases with poor prognostic criteria,> 3 lesions and / or size> 5 cm. Patients with a diagnosis of liver metastases with synchronous presentation or with a disease-free interval may be included. 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 transfused before 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 Ureic Nitrogen (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 informed consent to participate in the study
  • Women of childbearing potential must commit to sexual abstinence or use of barrier contraceptive methods during the study and must have a negative pregnancy test.

Exclusion Criteria:

  • Extension of the disease> 50% of the liver parenchyma (evaluated by CT performed within the month prior to inclusion)
  • Previous chemotherapy treatment for metastatic colorectal cancer
  • Clinically significant cardiovascular diseases: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure of New York Heart Association (NYHA) grade II or higher or severe cardiac arrhythmia.
  • History of malignancy in the last three years, except for basal cell carcinoma of the skin 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 of the study drug or with allergies to some of the drugs used
  • Pregnant or lactating patients
  • Portal thrombosis
  • Severe portal hypertension
  • Extrahepatic metastases

Sites / Locations

  • Hospital Parc TaulíRecruiting
  • Hospital Universitario de AlicanteRecruiting
  • Hospital ClínicRecruiting
  • Hospital de la Santa Creu i Sant PauRecruiting
  • Hospital Universitario 12 de OctubreRecruiting
  • Hospital Universitario La Paz
  • Complejo Hospitalario de NavarraRecruiting
  • Hospital Universitario de CanariasRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Control

Experimental

Arm Description

Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab).

Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab) + 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.

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
The proportion of patients with tumor size reduction according to RECIST 1.1 criteria at 6 months

Secondary Outcome Measures

Overall Survival (OS)
Time from randomization until death from any cause. Patients still alive at the last contact or lost to follow-up will be censored.
Progression free survival
Time from from the date of randomization to the date of first documented disease progression according to RECIST 1.1 criteria or the date of death due to any cause. Patients without radiological documentation of progression will be censored on the date of the last control without evidence of progression.
Frequency of adverse events
Percentage of adverse events, laboratory alterations and treatment discontinuations observed in both treatment arms classified by type and severity (Safety)
Hepatic Progression free survival
Time from from the date of randomization to the date of first documented disease progression within the liver according to RECIST 1.1 criteria or the date of death due to any cause. Patients without radiological documentation of progression will be censored on the date of the last control without evidence of progression.
Proportion of patients with liver surgery
Proportion of patients undergoing R0 surgery for liver metastases

Full Information

First Posted
October 6, 2020
Last Updated
February 22, 2023
Sponsor
Grupo Espanol Multidisciplinario del Cancer Digestivo
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1. Study Identification

Unique Protocol Identification Number
NCT04595266
Brief Title
Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease
Acronym
LIVERPEARL
Official Title
Randomized, Multicenter Phase II Study of Monoclonal FOLFOX6m + mAb Alone or in Combination With Liver Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease Limited to the Liver With Poor Prognosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 29, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Espanol Multidisciplinario del Cancer Digestivo

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer Metastatic, Liver Metastasis Colon Cancer
Keywords
Colorectal cancer, Chemoembolization, LIVERPEARLS-Irinotecan, Liver metastasis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Patients will be randomized in a 1: 1 ratio in the 2 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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Control
Arm Type
Active Comparator
Arm Description
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab).
Arm Title
Experimental
Arm Type
Experimental
Arm Description
Systemic chemotherapy with FOLFOX6m + monoclonal Ab (anti-EGFR or bevacizumab) + 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.
Intervention Type
Drug
Intervention Name(s)
FOLFOX regimen
Other Intervention Name(s)
Leucovorin/Fluorouracil/Oxaliplatin
Intervention Description
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
Intervention Type
Biological
Intervention Name(s)
Anti-EGFR or Bevacizumab
Other Intervention Name(s)
monoclonal antibody anti EGFR (RASwt) or Bevacizumab (RASmut)
Intervention Description
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. Treatment administered following Summary of medicinal Product Characteristics (SmPC) approved indications.
Intervention Type
Drug
Intervention Name(s)
LIVERPEARLS-Irinotecan
Other Intervention Name(s)
Chemoembolization of Irinotecan in hydrogel microspheres
Intervention Description
Chemoembolization of Irinotecan in 100 +/- 50 micron hydrogel microspheres. Irinotecan will be loaded at a dose of 100 mg. LIFEPEARLS® is a CE marked medical device consisting of microspheres for use in chemoembolization. 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.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
The proportion of patients with tumor size reduction according to RECIST 1.1 criteria at 6 months
Time Frame
Evaluated at 6 months after first investigation drug administration.
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
Time from randomization until death from any cause. Patients still alive at the last contact or lost to follow-up will be censored.
Time Frame
Through study completion, average 2 years
Title
Progression free survival
Description
Time from from the date of randomization to the date of first documented disease progression according to RECIST 1.1 criteria or the date of death due to any cause. Patients without radiological documentation of progression will be censored on the date of the last control without evidence of progression.
Time Frame
Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks
Title
Frequency of adverse events
Description
Percentage of adverse events, laboratory alterations and treatment discontinuations observed in both treatment arms classified by type and severity (Safety)
Time Frame
Through study completion, average 2 years
Title
Hepatic Progression free survival
Description
Time from from the date of randomization to the date of first documented disease progression within the liver according to RECIST 1.1 criteria or the date of death due to any cause. Patients without radiological documentation of progression will be censored on the date of the last control without evidence of progression.
Time Frame
Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks
Title
Proportion of patients with liver surgery
Description
Proportion of patients undergoing R0 surgery for liver metastases
Time Frame
Through study completion, average 2 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged ≥ 18 years. Patients with colorectal cancer and exclusive liver metastases with poor prognostic criteria,> 3 lesions and / or size> 5 cm. Patients with a diagnosis of liver metastases with synchronous presentation or with a disease-free interval may be included. 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: Hemoglobin ≥ 9.0 g / dl (patients with hemoglobin <9 g / dl can be transfused before inclusion in the study Platelet count ≥ 100 x 109 / L Absolute Neutrophil Count (ANC) ≥ 1.5x 109 / L Adequate liver function, according to: Serum bilirubin ≤ 1.5 x the upper limit of normal (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN. Alkaline phosphatase ≤ 5 x ULN or ≤10 x ULN in the presence of bone metastases Adequate renal function, with creatinine levels <1.5 mg / dL. Blood Ureic Nitrogen (BUN)> 50 ml / min. Albumin> 3.0 g / dL Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. Patients capable of understanding the information and giving their written informed consent to participate in the study Women of childbearing potential must commit to sexual abstinence or use of barrier contraceptive methods during the study and must have a negative pregnancy test. Exclusion Criteria: Extension of the disease> 50% of the liver parenchyma (evaluated by CT performed within the month prior to inclusion) Previous chemotherapy treatment for metastatic colorectal cancer Clinically significant cardiovascular diseases: cerebrovascular accident / stroke (≤ 6 months before inclusion in the trial), myocardial infarction (≤ 6 months before inclusion in the trial), unstable angina, uncontrolled hypertension, congestive heart failure of New York Heart Association (NYHA) grade II or higher or severe cardiac arrhythmia. History of malignancy in the last three years, except for basal cell carcinoma of the skin 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 of the study drug or with allergies to some of the drugs used Pregnant or lactating patients Portal thrombosis Severe portal hypertension Extrahepatic metastases
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Federico Nepote
Phone
934344412
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name or Official Title & Degree
Verónica Roca
Phone
934344412
Email
investigacion@mfar.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Estela Pineda, M.D
Organizational Affiliation
Hospital Clinic of Barcelona
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
David Páez, M.D., Ph.D.
Organizational Affiliation
Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Official's Role
Study Chair
Facility Information:
Facility Name
Hospital Parc Taulí
City
Sabadell
State/Province
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Hospital Universitario de Alicante
City
Alicante
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Hospital Clínic
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Investigator Selected by Sponsor
Facility Name
Hospital de la Santa Creu i Sant Pau
City
Barcelona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Hospital Universitario 12 de Octubre
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Hospital Universitario La Paz
City
Madrid
Country
Spain
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Complejo Hospitalario de Navarra
City
Pamplona
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Facility Name
Hospital Universitario de Canarias
City
Tenerife
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor
Email
investigacion@mfar.net
First Name & Middle Initial & Last Name & Degree
Principal Investigator Selected by Sponsor

12. IPD Sharing Statement

Learn more about this trial

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

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