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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 40um Embozene TANDEM Microspheres | Experimental | 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 40um Embozene TANDEM Microspheres | Device | 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg). |
|
| 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 |
| 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. |
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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:
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:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Franco Orsi, MD | European Institute of Oncology (Milan Italy) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| European Institute of Oncology | Milan | 20141 | Italy |
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Twenty MIRACLE III subjects were consented. Of these 20, eighteen (18) were enrolled and treated in the trial. Two subjects were not enrolled as they did not meet I/E criteria. These two subjects have been reported as screen failures.
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| ID | Title | Description |
|---|---|---|
| FG000 | 40um Embozene TANDEM Microspheres | 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg) 40um Embozene TANDEM Microspheres: 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg). |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
A total of 20 patients were consented to participate however, 2 patients were not enrolled as they were reported as screen failures prior to the first study treatment. Therefore a total of 18 baseline patients were assessed.
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| ID | Title | Description |
|---|---|---|
| BG000 | 40um Embozene TANDEM Microspheres | 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg) 40um Embozene TANDEM Microspheres: 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | 30 days |
|
Up to 24 months post procedure
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 40um Embozene TANDEM Microspheres | 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg) 40um Embozene TANDEM Microspheres: 40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Progression of Disease | Hepatobiliary disorders | Systematic Assessment | Progression of Disease leading to death |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post Embolization Syndrome | General disorders | Systematic Assessment | Abdominal Pain, Nausea, Fatigue & Fever |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Angela Schutt | Boston Scientific | 763-494-2166 | angela.schutt@bsci.com |
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| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
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| Up to 12 months post procedure |
| Screen Failure |
|
| Physician Decision |
|
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Eastern Cooperative Oncology Group (ECOG) Performance Score | ECOG 0 - Fully active, able to carry out all pre-disease performance without restriction. ECOG 1 - Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, e.g. light house work, office work. ECOG 2 - Ambulatory and capable of all self care, but unable to carry out any work activities. Up and about more than 50% of waking hours. ECOG 3 - Capable of only limited self care, confined to bed or chair more than 50% of waking hours. ECOG 4 - Completed disabled. Cannot carry out any self care. Totally confined to bed or chair. ECOG 5 -Dead | Count of Participants | Participants |
|
| Classification of Malignant Tumours (TNM) Stage | TNM staging takes into account the size of the tumour, whether the lymph nodes (glands) are affected and whether cancer cells have spread anywhere else. TNM stands for Tumour, Node, Metastasis. The TNM system describes the size of a primary tumour (T), whether the cancer has spread to the lymph nodes (N), and whether the cancer has spread to a different part of the body (M - for metastases). | Count of Participants | Participants |
|
| Child Pugh | The Pugh-Child score is measured utilizing five clinical measures. The five measures are: total bilirubin (yellow compound in bile from hemoglobin breakdown), serum albumin (blood protein produced in the liver), prothrombin time (time for blood to clot), ascites (fluid in peritoneal cavity), and hepatic encephalopathy (brain disorder from liver disease). A score of 1, 2, or 3 is given to each measure, with 3 being the most severe. From these assessments, Child-Pugh is scored as follows: Class A (5 to 6 points), Class B (7 to 9 points), and Class C (10 to 15 points) | Count of Participants | Participants |
|
| History of Radiotherapy | Count of Participants | Participants |
|
| History of Surgical Therapy | Count of Participants | Participants |
|
| History of Systemic Therapy | Count of Participants | Participants |
|
| Previous Lines of Chemotherapy | Count of Participants | Participants |
|
| Units | Counts |
|---|
| Participants |
|
|
| Primary | 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). | All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery. | Posted | Count of Participants | Participants | 3 months post procedure |
|
|
|
| Primary | 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). | All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery. | Posted | Count of Participants | Participants | 6 months post procedure |
|
|
|
| Primary | 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). | All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery. | Posted | Count of Participants | Participants | 12 months post procedure |
|
|
|
| Secondary | Survival Rate | Number of participants that were alive 12 months after their first study treatment. | Posted | Count of Participants | Participants | 12 months post procedure |
|
|
|
| Secondary | 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. | Two participants that did not have disease progression reported during the trial are not included in this analysis. One subject underwent liver resection surgery after their third study treatment and another subject's tumor response was reported as stable disease prior to being lost to follow up after their third study treatment. | Posted | Mean | Standard Deviation | days | Up to 12 months post procedure |
|
|
|
| 10 |
| 18 |
| 10 |
| 18 |
| 17 |
| 18 |
|
|
| Decreased Liver Function | Hepatobiliary disorders | Systematic Assessment | Total Bilirubin Increase |
|
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Allergic Reaction | Immune system disorders | Systematic Assessment | Allergic Reaction to Contrast Media |
|
| Asthenia | General disorders | Systematic Assessment | Abnormal physical weakness or lack of energy |
|
| Atrial Fibrillation | Cardiac disorders | Systematic Assessment |
|
| Anorexia | General disorders | Systematic Assessment |
|
| Bone Fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment | The presence of abnormally few neutrophils in the blood, leading to increased susceptibility to infection |
|
| Edema | General disorders | Systematic Assessment | A condition characterized by an excess of watery fluid collecting in the cavities or tissues of the body. |
|
| Access Site Haemorrhage | Surgical and medical procedures | Systematic Assessment |
|
| Hypochondrium Pain | General disorders | Systematic Assessment | Abdominal pain |
|
| Visual Impairment | Eye disorders | Systematic Assessment | Accommodation Disorder |
|
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| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |