Clinical trial NCT04595266: Chemoembolization (Lifepearls-Irinotecan) in Patients With Colorectal Cancer and Metastatic Disease
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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Liver Metastasis Colon Cancer
Keywords: Colorectal cancer
Chemoembolization
LIVERPEARLS-Irinotecan
Liver metastasis
Lead sponsor: Grupo Espanol Multidisciplinario del Cancer Digestivo
Sponsor class: OTHER
First posted: 2020-10-20
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Evaluated at 6 months after first investigation drug administration.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Through study completion, average 2 years
measure: Progression free survival
timeFrame: Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks
measure: Frequency of adverse events
timeFrame: Through study completion, average 2 years
measure: Hepatic Progression free survival
timeFrame: Through study completion, average 2 years. Evaluated during a total of 2 years (estimated) by CT scan or MR every 12 weeks
measure: Proportion of patients with liver surgery
timeFrame: Through study completion, average 2 years.
Other outcomes:
Locations:
city: Sabadell
country: Spain
facility: Hospital Parc Taulí
state: Barcelona
city: Alicante
country: Spain
facility: Hospital Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital Clínic
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: H. Univ. Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Pamplona
country: Spain
facility: Complejo Hospitalario de Navarra
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Estela Pineda, M.D
role: STUDY_CHAIR
affiliation: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
name: David Páez, M.D., Ph.D.
role: STUDY_CHAIR
References: