Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy (MIRACLEIII)

Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy: A Pilot Study of Irinotecan in the Treatment of Metastatic Colorectal Carcinoma (mCRC) by Embozene TANDEM™ Drug-Eluting Microspheres Embolization

The purpose of this study is to determine safety and local tumor control of Embozene TANDEM Microspheres (40um TANDEM) loaded with Irinotecan to treat metastatic colorectal carcinoma (mCRC).

Study Overview

• Status: Completed
• Conditions: Colorectal Carcinoma
• Intervention / Treatment: Device: 40um Embozene TANDEM Microspheres

Detailed Description

Colon or rectal carcinoma that has spread to the liver is considered to be metastatic and is a Stage IV cancer. If the metastasized tumor is unresectable, the only current treatment is chemotherapy. Transarterial Chemoembolization (TACE) is considered as a palliative treatment in advanced metastatic colorectal carcinoma (mCRC), with the potential of local tumor control. TACE has evolved in the past 8 years to include drug-delivery devices that can target and deliver drugs from small microparticles (DEB-TACE). Superselective DEB-TACE has the potential to penetrate deeper into the tumor's vasculature to reach peripheral growing points. Loading these microparticles with a cytotoxic drug may improve the level of local tumor control.

The MIRACLE III study is a controlled, pilot, single center (Italy) study on 18 subjects with pretreated non-resectable mCRC.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Milan, Italy, 20141
    • European Institute of Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female, age >18 yrs who have histologically confirmed adenocarcinoma of the colon or rectum (Stage IV)
• Presence of metastatic disease with liver as dominant disease-site defined as >80% tumor body burden confined to liver; less than 60% liver tumor replacement.
• Subject is competent and willing to provide written informed consent in order to participate in the study.
• Eastern Cooperative Oncology Group (ECOG) performance status is 0-1 or Child-Pugh classification is A or B7.
• Multinodular or single nodular tumor 4 cm, patients with bilobar disease who can be treated superselectively in a single session or both lobes able to be treated within 3 weeks. Patient must have at least one tumor lesion that meets the following criteria: lesion can be accurately measured in at least one dimension according to the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.
• Pretreatment with two or more lines of chemotherapy containing Fluorouracil (5-FU) or analogue, oxaliplatin, irinotecan ± bevacizumab ±epidermal growth factor receptor (EGFR)-inhibitors, if indicated, for metastatic disease.
• No invasion in the blood vessel (hepatic portal, hepatic vein) or bile duct by the computerized axial tomography (CT) or Magnetic Resonance (MR) Imaging.

• Proper blood, liver, renal, heart function: testing result within 2 weeks from registry of this study as follows:

  1. White Blood Cell (WBC) >3,000 cells/mm3
  2. Absolute neutrophil count ≥1500/mm3
  3. International Normalized Ratio (INR) <2.0
  4. Partial Thromboplastin Time (PTT) <40 sec
  5. Platelet count >50,000/mm3
  6. Blood bilirubin <3.0 mg/dL
  7. Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) is within 5 times of normal range of each organ
  8. Serum creatinine <1.5 mg/dL
  9. Hemoglobin >8.0 g/dL
  10. Alkaline phosphatase <630 IU/L
  11. No unstable coronary artery disease or recent Myocardial Infarction(MI)
  12. Normal electrocardiogram (ECG) with QT interval <480 msec within the previous 12 months
  13. No current infections requiring antibiotic therapy
  14. Not on anticoagulation or suffering from a known bleeding disorder.
• Measureable disease per mRECIST.
• Expected survival more than 3 months

Exclusion Criteria:

• ECOG performance status >2; or Child-Pugh class>11 points or more, or American Society of Anaesthesiologists' (ASA) class 5 .
• Bilirubin levels >3 mg/dL
• mCRC within the large vessel or biliary duct invasion, diffuse hepatocellular carcinoma (HCC) or extrahepatic spread.

• Patients in which any of the following are contraindicated or present:

  1. The use of irinotecan
  2. MRI or CT scans
  3. Hepatic embolization procedures
  4. WBC <3000 cells/mm3
  5. neutrophil <1500 cells/mm3
  6. Cardiac ejection fraction <50% assessed by isotopic ventriculography, echocardiography or MRI
  7. Elevated serum creatinine ≥ 2.5 mg/dL
  8. Impaired clotting test (platelet count < 50,000/mm3, PT-INR >2.0
  9. AST and/or ALT >5x upper limit of normal (ULN), when greater >250 U/I
  10. Known hepatofugal blood flow.
  11. Arterio-venous shunt
  12. Arterio-portal shunt
  13. Main stem portal vein occlusion
• Women who are pregnant or nursing
• Allergy to iodinated contrast used for angiography
• Tumour burden of more than 50% of liver volume (Tumor volume by be smaller e.g. ≤30%)
• Patients with active bacterial, viral (HIV), or fungal infection.
• Other malignancies
• Any co-morbid disease or condition or event that, in the investigator's judgment, would place the patient a undue risk what would preclude the safe use of DEB-TACE.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 40um Embozene TANDEM Microspheres; 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg)	Device: 40um Embozene TANDEM Microspheres; 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom From Serious Adverse Events Rate	Freedom from Serious Adverse Events reports the number of participants that did not have a serious adverse event reported within 30 days of treatment that results in any of the following outcomes: Death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defects.	30 days
Local Tumor Control	Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria).	3 months post procedure
Local Tumor Control	Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria).	6 months post procedure
Local Tumor Control	Local tumor control reports the percent of subjects for which the size of the tumor does not increase. Local Tumor Control is defined as subjects having complete response or stable disease. For these subjects the treated tumor either shrinks or stays the same size when measuring the tumor using a standard tumor measurement guideline (based on the devascularization pattern from the European Association for the Study of the Liver (EASL) criteria).	12 months post procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival Rate	Number of participants that were alive 12 months after their first study treatment.	12 months post procedure
Time To Tumor Progression	Time to Tumor Progression is defined as the time from the date of first study treatment to the day of documented disease progression or death due to any cause, whichever came first, assessed up to 1 year. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (mRECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	Up to 12 months post procedure

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Franco Orsi, MD, European Institute of Oncology (Milan Italy)

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2013
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: February 25, 2016
• First Submitted That Met QC Criteria: February 25, 2016
• First Posted (Estimate): February 29, 2016

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: September 27, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Metastatic Colorectal Carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Carcinoma; Colorectal Neoplasms
• Other Study ID Numbers: MIRACLE III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No