Clinical trial NCT02694562: Microparticle Enhanced Cytotoxic Transarterial Embolization Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Colorectal Carcinoma
Keywords: Metastatic Colorectal Carcinoma
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2016-02-29
Enrollment: 18
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Freedom From Serious Adverse Events Rate
timeFrame: 30 days
measure: Local Tumor Control
timeFrame: 3 months post procedure
measure: Local Tumor Control
timeFrame: 6 months post procedure
measure: Local Tumor Control
timeFrame: 12 months post procedure
Secondary outcomes:
measure: Survival Rate
timeFrame: 12 months post procedure
measure: Time To Tumor Progression
timeFrame: Up to 12 months post procedure
Other outcomes:
Locations:
city: Milan
country: Italy
facility: European Institute of Oncology
Study officials:
affiliation: European Institute of Oncology (Milan Italy)
name: Franco Orsi, MD
role: PRINCIPAL_INVESTIGATOR
References: