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Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI).

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ClinicalTrials.gov Identifier: NCT02350400
Recruitment Status : Completed
First Posted : January 29, 2015
Last Update Posted : February 14, 2017
Sponsor:
Collaborator:
Singhealth Foundation
Information provided by (Responsible Party):
Singapore General Hospital

Brief Summary:

Background

Hepatic metastases of colorectal cancer (MCC) is quite common and is a major source of morbidity and mortality. There has been evidence to show that hepatic arterial chemoembolisation using DC beads (drug eluting beads, 100-300μm) loaded with irinotecan (DEBIRI) showed improved overall survival when compared to systemic therapy (FOLFIRI), but being larger they have their limitations.

New 70-150μm beads are recently available and currently there is limited data concerning its use. Safety of these beads have not been tested in local patients.

Hypothesis / Aim To study the safety and pharmacokinetics of the smaller 70-150μm DEBIRI in a pilot study of 5 patients. The smaller 70-150μm beads will be able to deliver a more consistent and higher dose to tumoral tissue with a smaller systemic dose. Being smaller and less embolic, it will also be better tolerated. Patients will also be genotyped for their UGT1A1*28 and UGT1A1*6 polymorphism status as the latter genotypes are associated with decreased clearance of irinotecan and SN-38 in Asian patients.

Methods Single centre, pilot study, prospectively recruiting 5 patients with unilobar disease, refractory to systemic chemotherapy

The primary endpoints:

  1. establish safety and toxicity profile of the irinotecan loaded DEBIRI beads
  2. establish pharmacokinetics and systemic exposure of irinotecan and its active metabolite, SN-38.

The secondary outcome measurements:

  1. the incidence and severity of adverse events, liver function parameters and laboratory abnormalities;
  2. response rate,
  3. progression free survival
  4. overall survival

Clinical Significance

This treatment modality has the advantage of directly delivering irinotecan to the liver metastases from colorectal cancer. This local mode of drug delivery may result in a higher intratumoral drug concentration and rapid tumour shrinkage leading to downstaging of the hepatic metastatic lesions. These therapeutic outcomes may also downstage patients to hepatic resection.


Condition or disease Intervention/treatment Phase
Colorectal Cancer Metastatic Device: DEBIRI Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pilot Study to Assess the Safety and Pharmacokinetics of 70-150μm Drug Eluting Beads Loaded With Irinotecan (DEBIRI) in the Treatment of Hepatic Colorectal Metastases
Study Start Date : June 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DEBIRI
For unilobar disease, two treatments will be planned, separated by four weeks. For bilobar disease, there will be four treatments planned, alternating between right and left lobe, separated by 2 weeks duration.
Device: DEBIRI
DEBIRI TACE
Other Names:
  • DC Beads loaded with irinotecan
  • (Manufacturer- Biocompatibles UK Limited)




Primary Outcome Measures :
  1. Establish safety and toxicity profile of the irinotecan loaded DEBIRI beads (number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials) [ Time Frame: 1 year ]
    By looking at the number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials (June 2011)


Secondary Outcome Measures :
  1. Tumour response (measured by mRECIST) [ Time Frame: 6 months ]
    measured by mRECIST



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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Metastatic colorectal carcinoma to the liver, both unilobar and bilobar disease
  2. Refractory to 1st or 2nd line systemic chemotherapy. Previous chemotherapy had to be discontinued at least 4 weeks prior to study entry
  3. Hepatic disease should be 80% or more of total body tumor burden
  4. Measurable liver tumour burden was of no more than 60% of the total liver volume.
  5. A performance status of 0-2 (WHO criteria).
  6. Age <85 years were required.
  7. Life expectancy of greater than 3 months
  8. Adequate hematologic function (granulocyte count ≥ 1.5 × 109/L, platelet count ≥ 100 × 109/L, INR ≤ 1.3 in patients on anticoagulant therapy)Adequate hepatic function (total bilirubin ≤ 1.5 x the upper limits of normal [ULN], AST and ALT ≤ 5 x ULN, and alkaline phosphatases < 5 x ULN) and,
  9. Adequate renal function (creatinine clearance > 50 mL/min)

Exclusion Criteria:

  1. Extrahepatic tumor burden of > 20%.
  2. Patients with unilobar disease who are candidates for surgical resection.
  3. Extensive tumor involvement of the liver (>60%)
  4. Poor performance status (>2 WHO criteria)
  5. Significant diseases of cardiac, renal, bone marrow or pulmonary apparatus, central nervous system involvement, and uncontrolled infection
  6. Liver function tests and bilirubin 5-folds more than the normal value
  7. History of other cancer except adequately treated in situ carcinoma of the cervix or basal or squamous carcinoma of the skin
  8. Absolute neutrophil count of less than 1500 cells/µL
  9. Platelet count of less than 100,000/µL
  10. Significant portal vein thrombosis
  11. Unable to understand nature of study and provide written consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02350400


Locations
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Singapore
Singapore General Hospital
Singapore, Singapore, 169608
National Cancer Centre Singapore
Singapore, Singapore, 169610
Sponsors and Collaborators
Singapore General Hospital
Singhealth Foundation
Investigators
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Principal Investigator: Kiang Hiong Tay, MBBS FRCR Singapore General Hospital

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Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT02350400     History of Changes
Other Study ID Numbers: DEBIRI_TKH_01_2012
First Posted: January 29, 2015    Key Record Dates
Last Update Posted: February 14, 2017
Last Verified: February 2017

Keywords provided by Singapore General Hospital:
Drug eluting beads
Irinotecan
Pharmacogenetics
Pharmacokinetics

Additional relevant MeSH terms:
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Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents