Colorectal Carcinoma
Conditions
Keywords
Metastatic Colorectal Carcinoma
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.
Interventions
DEVICE40um Embozene TANDEM Microspheres
40um Embozene TANDEM Microspheres loaded with Irinotecan (up to 150 mg).
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From Serious Adverse Events Rate | 30 days | 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. |
| Local Tumor Control | 3 months post procedure | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate | 12 months post procedure | Number of participants that were alive 12 months after their first study treatment. |
| Time To Tumor Progression | Up to 12 months post procedure | 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. |
Countries
Italy
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 8 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Screen Failure | 2 |
Baseline characteristics
| Characteristic | 40um Embozene TANDEM Microspheres |
|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 10.1 |
| Child Pugh Child Pugh - A | 17 Participants |
| Child Pugh Child Pugh - B7 | 0 Participants |
| Child Pugh Not Available | 1 Participants |
| Classification of Malignant Tumours (TNM) Stage TNM Stage I | 0 Participants |
| Classification of Malignant Tumours (TNM) Stage TNM Stage II | 0 Participants |
| Classification of Malignant Tumours (TNM) Stage TNM Stage III | 0 Participants |
| Classification of Malignant Tumours (TNM) Stage TNM Stage IV | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Score ECOG Score 0 | 18 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Score ECOG Score 1 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Score ECOG Score 2 | 0 Participants |
| History of Radiotherapy | 2 Participants |
| History of Surgical Therapy | 16 Participants |
| History of Systemic Therapy | 18 Participants |
| Previous Lines of Chemotherapy Participants with 1 Previous Line of Chemotherapy | 0 Participants |
| Previous Lines of Chemotherapy Participants with 2 Previous Lines of Chemotherapy | 2 Participants |
| Previous Lines of Chemotherapy Participants with 3 Previous Lines of Chemotherapy | 5 Participants |
| Previous Lines of Chemotherapy Participants with 4 Previous Lines of Chemotherapy | 5 Participants |
| Previous Lines of Chemotherapy Participants with 5 Previous Lines of Chemotherapy | 5 Participants |
| Previous Lines of Chemotherapy Participants with 6 Previous Lines of Chemotherapy | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment Italy | 18 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 18 |
| other Total, other adverse events | 17 / 18 |
| serious Total, serious adverse events | 10 / 18 |
Outcome results
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.
Time frame: 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40um Embozene TANDEM Microspheres | Freedom From Serious Adverse Events Rate | 18 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).
Time frame: 3 months post procedure
Population: All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40um Embozene TANDEM Microspheres | Local Tumor Control | 15 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).
Time frame: 6 months post procedure
Population: All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40um Embozene TANDEM Microspheres | Local Tumor Control | 7 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).
Time frame: 12 months post procedure
Population: All subjects were included in this analysis except for one subject that was removed from the study after undergoing liver resection surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40um Embozene TANDEM Microspheres | Local Tumor Control | 3 Participants |
Secondary
Survival Rate
Number of participants that were alive 12 months after their first study treatment.
Time frame: 12 months post procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 40um Embozene TANDEM Microspheres | Survival Rate | 10 Participants |
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.
Time frame: Up to 12 months post procedure
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 40um Embozene TANDEM Microspheres | Time To Tumor Progression | 177.2 days | Standard Deviation 111.4 |