Clinical trial NCT02015754: Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer
Official title: Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2013-12-19
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Purpose:

The purpose of this study is to determine the feasibility and safety of using small beads (70-150 micron in place of 100-300 micron) to deliver chemotherapy into the liver to treat patients with liver lesions from colorectal cancer. The beads (LC-Bead M1) will be loaded with irinotecan (DEBIRI-M1), and used to administer transarterial chemoembolization (TACE).

Eligibility:

Patients with liver cancer from colorectal cancer.

Study Overview/ Treatment:

DEBIRI, loaded with irinotecan, is a device that utilizes tiny beads (70-150 microns) to deliver chemotherapy agents into liver tumor(s) via the hepatic artery. This device allows for continuous release of irinotecan into the liver tumor tissue(s) causing necrosis of the targeted tumor(s). The potential advantages of the smaller beads are deeper penetration into the tumor bed, while avoiding premature proximal occlusion of vessels feeding the tumor, and more consistent dosing. Response to therapy will be evaluated monthly by clinic visits and blood tests (to include assessment of liver function and tumor markers) and by imaging (usually MRIs) every 1-2 months. Patients will be on study for 6 months after which they will be exited from the study and followed for survival. Once exited from the study they will continue to be eligible to receive DEBIRI, should it be recommended.


Eligibility criteria: Inclusion Criteria:

-Patients with a diagnosis of colorectal cancer with hepatic metastases who have failed or are intolerant to at least one systemic chemotherapy or liver directed therapy.

1. The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at study entry.
2. The patient is age 18 years or older.
3. The patient has a life expectancy of \>12 weeks.
4. Patients with liver dominant disease defined as \>/=75% tumor body burden confined to the liver
5. Less than 60% liver tumor replacement
6. At least one month has elapsed since most recent prior cancer therapy with the following exception:

   -Chemotherapy (excluding irinotecan based regimens) may continue if there is evidence of hepatic progression on treatment providing there is no change in the therapy in the 1 month prior to DEBIRI-TACE treatment and any immediate chemotherapeutic toxicity that will complicate DEBIRI-TACE is resolved. In this case, the chemotherapy may continue because it is continuing to control the extrahepatic disease.
7. The patient has measurable disease that will be directly treated with intrahepatic therapy (as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1).
8. Patients with at least one measurable liver metastases\> 2 cm.
9. Patients with patent main portal vein
10. The patient has adequate hematologic function as defined by the following criteria:

    -An absolute neutrophil count (ANC) \>/= 1500/mL, Hemoglobin \>/= 9.5 g/dL, and a Platelet count \>/=75,000/mL, INR \</=1.3 prior to receiving DEBIRI-TACE.
11. The patient has adequate hepatic function, as defined by the following criteria:

    -Total bilirubin\</= 2.0 mg/dL, Aspartate transaminase (AST) and alanine transaminase (ALT) \</= 5 x the upper limit of normal (ULN), Albumin \>2.
12. The patient has adequate renal function, as defined by the following criteria:

    -Serum creatinine\</=2.0.
13. The patient has a baseline international normalized ratio (INR)\<1.5.
14. The patient, if a woman of childbearing potential, has a negative pregnancy test.
15. The patient is able to give written informed consent.
16. The patient is willing and able to comply with study procedures, scheduled visits, and treatment plans.

Exclusion Criteria:

1. The patient has a history of another primary cancer (ie, a primary cancer not associated with the patient's current liver tumor), with the exception of (a) curatively resected nonmelanomatous skin cancer; (b) curatively treated cervical carcinoma in situ; or (c) other primary solid tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years prior to enrollment (date of informed consent).
2. Any contraindication for hepatic embolization procedures:

   * Large shunt as determined by the investigator (pretesting with TcMMA not required)
   * Severe atheromatosis
   * Hepatofugal blood flow
   * Main portal vein occlusion (e.g. thrombus or tumor)
   * Any patient eligible for curative treatment (i.e. resection or radiofrequency ablation)
   * Patients' whose only measurable disease is within an area of the liver previously subject to radiotherapy
3. Contraindications to irinotecan:

   * Chronic inflammatory bowel disease and/or bowel obstruction
   * History of severe hypersensitivity reactions to irinotecan hydrochloride trihydrate, lactic acid or to any of the excipients of Camptosar
   * Severe bone marrow failure
   * History of Gilbert Syndrome (specific testing not required)
   * Concomitant use with St John's Wort (Hypericum)
   * Marco-shunting noted on the hepatic angiogram.
4. The patient has untreatable bleeding diathesis.
5. The patient has complete main portal vein thrombosis with reversal of flow.
6. The patient has evidence of clinically significant peripheral vascular disease.
7. The patient has brain metastases
8. The patient has clinically significant or symptomatic extrahepatic disease, for example, an uncontrolled intercurrent illness including, but not limited to:

   * Ongoing or active infection requiring parenteral antibiotics
   * Symptomatic congestive heart failure (class II to IV of the New York Heart Association classification for heart disease)
   * Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
   * Uncontrolled hypertension (systolic blood pressure\>150 mmHg, diastolic blood pressure\>90 mmHg, found on 2 consecutive measurements separated by a 1-week period despite adequate medical support)
   * Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment \[NCI-CTCAE Grade 3\] or asymptomatic sustained ventricular tachycardia)
9. The patient is pregnant or breast-feeding.
10. Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements
11. There is evidence of substance abuse or medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of study results
12. The patient is allergic to contrast media that cannot be readily prevented with premedication or managed.
13. Other significant medical or surgical condition, or any medication or treatment, that would place the patient at undue risk and that would preclude the safe use of chemoembolization or would interfere with study participation
14. The patient has peritoneal disease or ascites (greater than trace on imaging).

Primary outcomes:
measure: Success of DEBIRI-M1 Procedure as a Measure of Feasibility (Percentage of Successful Treatments)
timeFrame: 6 months
measure: Safety, Defined as Demonstrating Tolerable Device-related Toxicity Profile in the Use of DEBIRI Beads Used to Treat Hepatic Metastases in Patients With Colorectal Cancer
timeFrame: 6 weeks
Secondary outcomes:
measure: Efficacy - Tumor Response by RECIST
timeFrame: 24 weeks
measure: Efficacy - Tumor Response by mRECIST
timeFrame: 24 weeks
measure: Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria
timeFrame: 24 weeks
measure: Efficacy - Tumor Response by World Health Organization (WHO) Criteria
timeFrame: 24 weeks
measure: Number of Participants With Change in Carcinoembryonic Antigen (CEA)
timeFrame: 6 weeks
measure: Median Overall Survival
timeFrame: Up to 26 months
measure: One-year Survival Percentage
timeFrame: 1 year
Other outcomes:
measure: Exploratory Endpoint - Pharmacokinetic (PK) Profile of Irinotecan and SN-38 Post DEBIRI-TACE
timeFrame: 24 hours
measure: Exploratory Endpoint -Total Drug Exposure Over Time (AUC) of Irinotecan and SN-38 Post DEBIRI-TACE
timeFrame: 24 hours
measure: Exploratory Endpoint -Tmax of Irinotecan and SN-38 Post DEBIRI-TACE
timeFrame: 24 hours
measure: Plasma Half-life of Irinotecan and SN-38 Post DEBIRI-TACE
timeFrame: 24 hours
measure: Exploratory Endpoint - Angiogenesis
timeFrame: 24 hours
Locations:
city: Baltimore
country: United States
facility: The Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: J.F. Geschwind, MD
role: PRINCIPAL_INVESTIGATOR
References: