Irinotecan -Eluting LC Bead-M1 (DEBIRI-M1) for Patients With Liver Metastases From Colorectal Cancer

NCT02015754 | Completed Phase 2 Results DMC

• 2 other identifiers: J1305NA_00078095 [JHMIRB]
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (2)

• Success of DEBIRI-M1 Procedure as a Measure of Feasibility (Percentage of Successful Treatments)

  Feasibility is defined as achieving an acceptable level of technical success in the use of DEBIRI beads treating hepatic metastases in patients with colorectal cancer.

  6 months

• 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

  Toxicities assessed as being at least possibly related will be recorded including system organ class, subclass, grade, frequency and time interval from DEBIRI-M1.

  6 weeks

Secondary Outcomes (7)

• Efficacy - Tumor Response by RECIST

  24 weeks

• Efficacy - Tumor Response by mRECIST

  24 weeks

• Efficacy -Tumor Response by European Association for the Study of the Liver (EASL) Criteria

  24 weeks

• Efficacy - Tumor Response by World Health Organization (WHO) Criteria

  24 weeks

• Number of Participants With Change in Carcinoembryonic Antigen (CEA)

  6 weeks

Other Outcomes (5)

• Exploratory Endpoint - Pharmacokinetic (PK) Profile of Irinotecan and SN-38 Post DEBIRI-TACE

  24 hours

• Exploratory Endpoint -Total Drug Exposure Over Time (AUC) of Irinotecan and SN-38 Post DEBIRI-TACE

  24 hours

• Exploratory Endpoint -Tmax of Irinotecan and SN-38 Post DEBIRI-TACE

  24 hours

Study Arms (1)

DEBIRI

EXPERIMENTAL

Drug: DEBIRI; Device: LC Bead M1; Procedure: TACE

Interventions

DEBIRI DRUG

Irinotecan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extracted from the tree Camptotheca acuminata. Irinotecan hydrochloride trihydrate is a pale yellow to yellow crystalline powder, it is mixed in DC Beads and injected in the tumor.

DEBIRI

LC Bead M1 DEVICE

The LC Bead M1, loaded with irinotecan (DEBIRI-M1) to treat patients with hepatic metastases from colorectal cancer.

DEBIRI

TACE PROCEDURE

TACE a minimally invasive procedure performed to restrict a tumor's blood supply.

DEBIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at study entry.
• The patient is age 18 years or older.
• The patient has a life expectancy of \>12 weeks.
• Patients with liver dominant disease defined as \>/=75% tumor body burden confined to the liver
• Less than 60% liver tumor replacement
• 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.
• 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).
• Patients with at least one measurable liver metastases\> 2 cm.
• Patients with patent main portal vein
• 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.
• 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.

You may not qualify if:

• 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).
• 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
• 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.

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Jean-Francois Geschwind, MD
• Organization: Yale University

jeff.geschwind@yale.edu

203-785-5865

Study Officials

• J.F. Geschwind, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2013
• First Posted: December 19, 2013
• Study Start: February 1, 2014
• Primary Completion: June 2, 2015
• Study Completion: December 13, 2016
• Last Updated: March 22, 2018
• Results First Posted: March 22, 2018

Record last verified: 2018-02

Locations

US (1)