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

NCT02350400 | Completed Phase 1 DMC

• 1 other identifier: DEBIRI_TKH_01_2012
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

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. 1.establish safety and toxicity profile of the irinotecan loaded DEBIRI beads
2. 2.establish pharmacokinetics and systemic exposure of irinotecan and its active metabolite, SN-38.
3. 3.the incidence and severity of adverse events, liver function parameters and laboratory abnormalities;
4. 4.response rate,
5. 5.progression free survival
6. 6.overall survival

Conditions

Colorectal Cancer Metastatic

Keywords

Drug eluting beads; Irinotecan; Pharmacogenetics; Pharmacokinetics

Outcome Measures

Primary Outcomes (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)

  By looking at the number of patients with adverse events according to Health Science Authority's Safety Reporting for Clinical Trials (June 2011)

  1 year

Secondary Outcomes (1)

• Tumour response (measured by mRECIST)

  6 months

Study Arms (1)

DEBIRI

EXPERIMENTAL

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

Interventions

DEBIRI DEVICE

DEBIRI TACE

Also known as: DC Beads loaded with irinotecan, (Manufacturer- Biocompatibles UK Limited)

DEBIRI

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic colorectal carcinoma to the liver, both unilobar and bilobar disease
• Refractory to 1st or 2nd line systemic chemotherapy. Previous chemotherapy had to be discontinued at least 4 weeks prior to study entry
• Hepatic disease should be 80% or more of total body tumor burden
• Measurable liver tumour burden was of no more than 60% of the total liver volume.
• A performance status of 0-2 (WHO criteria).
• Age \<85 years were required.
• Life expectancy of greater than 3 months
• 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,
• Adequate renal function (creatinine clearance \> 50 mL/min)

You may not qualify if:

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

Sponsors & Collaborators

• Singapore General Hospital: lead
• Singhealth Foundation: collaborator

Study Sites (2)

National Cancer Centre Singapore

Singapore, Singapore, 169610, Singapore

Location

Singapore General Hospital

Singapore, 169608, Singapore

Location

Study Officials

• Kiang Hiong Tay, MBBS FRCR

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2014
• First Posted: January 29, 2015
• Study Start: June 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: February 14, 2017

Record last verified: 2017-02

Locations

SG (2)