Clinical trial NCT00816777
Conditions: Unresectable Metastatic Colo-rectal Cancer
Keywords: Cancer Carcinoma Colon Cancer Colorectal Cancer Gastric Cancer Gastrointestinal Cancer Metastases Metastatic Cancer Metastatic Colorectal Cancer Oncology Rectal Cancer
Sponsor: Generic Devices Consulting, Inc.
Start date: 2008-12-01; Completion date: 2011-03-01
Enrollment: 4 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary objective of this study is to evaluate the safety and efficacy of Irinotecan Bead in combination with intravenous chemotherapy versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer. The results of this study are intended to be used in support of a PMA application for a combination device

Detailed description:
There are many treatments for metastatic colorectal cancer to the liver, and both the application and outcomes are highly dependant on the patients disposition. Whilst resection results in the best long term survival, it is often not a viable treatment option.

Irinotecan Bead is an embolization device intended to treat colorectal cancer metastases of the liver. As an adjunct to this, irinotecan is present in the microspheres which is released in a controlled manner into the local environment of the tumor. Irinotecan Bead is a combination of an approved embolization device and an approved chemotherapy agent. The device is a PVA based embolization agent from Biocompatibles UK Ltd, and the irinotecan is sourced from an FDA approved supplier.

Irinotecan, a topoisomerase inhibitor, was the first systemic chemotherapy drug other than 5-Fluorouracil (5-FU) to demonstrate significant activity in the treatment of metastatic colorectal cancer. Irinotecan is approved for use in combination with 5-FU/folinic acid in patients without prior chemotherapy, and for the second-line treatment of metastatic colorectal cancer as a single agent in patients who have failed an established 5-FU containing treatment regimen.

The purpose of this combination device as a treatment for cancer in the liver is twofold:

(i) Nutrient and oxygen starvation of the tumor. (ii) Minimization of chemotherapy wash-out with prolonged contact with tumor tissue.

Irinotecan Bead can be administered intra-arterially in the same manner as conventional TACE. The benefit of this product is that TACE is achieved in a simpler one-step procedure by precisely embolizing the arteries feeding the tumor, and as an ancillary action, the Irinotecan Bead may release a controlled dose of irinotecan into the tumor bed.

The potential benefits of Irinotecan Bead could be significant since a sustainable release of chemotherapy over time could have a greater effect on tumor mass, because optimal therapeutic efficacy of Irinotecan (an S phase-specific cytotoxic drug) generally requires prolonged exposure of the tumor to concentrations exceeding a minimum threshold.

Studies of low-dose, protracted administration of Irinotecan and other camptothecin analogues in mice bearing xenografts of human tumors have shown less toxicity and equal to or better antitumor activity than shorter, more intense dosing schedules. With the proposed device, the in-vivo and pre-clinical data shows that there is reduced systemic levels of Irinotecan, when delivered to tumorous tissue following embolization, and a longer, sustained concentration of the active metabolite, SN-38.

This is a multicentre, open labeled, prospective, randomized, controlled phase II study designed to assess the clinical performance of chemoembolization with Irinotecan Bead in combination with intravenous chemotherapy (irinotecan monotherapy) versus intravenous chemotherapy alone in the treatment of unresectable liver metastases in patients with colorectal cancer who previously failed first line chemotherapy.

The primary endpoint will be Progression Free Survival measured from the first treatment in this study until progression. Additional endpoints will be Pharmacokinetics of systemic Irinotecan and SN-38 (Irinotecan Bead treatment for feasibility group only); Tumor Response measured according to RECIST; Local tumor response (extent of necrosis in the treated lesions); hepatic progression free survival measured from first treatment until progression in the liver; change in tumor markers (CEA and optional CA19-9); performance status and overall survival assessed by telephone follow-up. Safety will be measured by assessing Adverse Events and Toxicity according to the NCI CTCAE v3.0 criteria.

Approximately 70 patients will be enrolled. The first 10 patients will be enrolled in a feasibility safety evaluation in the test arm of the trial.

Arms: arm 1: Chemoembolization with Irinotecan Bead in combination with Intravenous Chemotherapy Group (test arm) arm 2: Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks
Interventions: intervention 1: Chemoembolization with irinotecan Bead intervention 2: Irinotecan
Intervention descriptions: intervention 1: Intra arterial chemoembolization using Irinotecan Bead 100mg irinotecan per procedure in combination with irinotecan monotherapy 250mg/m2 alternating on a 3 weekly schedule intervention 2: Irinotecan monotherapy: 250mg/m2 repeated every 3 weeks

Protocol documents: