Unresectable Colorectal Liver Metastasis Clinical Trial
Official title:
A Prospective Open-label Study of Transarterial Chemoembolization by Hepasphere Microspheres for the Treatment of Unresectable Colorectal Liver Metastasis
Colorectal cancer is the third most frequently diagnosed cancer and the third leading cause
of cancer related deaths in Taiwan. Of the 10,248 new colorectal patients diagnosed each year
approximately 60% will develop liver metastasis during the course of their disease. In
approximately 30% of these patients who develop liver metastasis the metastatic disease will
remain confined to the liver.
For the 70-75% of colorectal patients with colorectal liver metastasis not suitable for
hepatic resection or similarly ablative therapy with curative intent, systemic chemotherapy
is the standard initial management. However, after a patient has failed first- line and in
some cases second-line chemotherapy, response rates fall to as low as 12% (Chen HX 2006).
Transarterial chemoembolization (TACE) with microsphere is an alternative treatment because
normal liver tissue receives most of its blood supply from the portal vein, while colorectal
liver metastases derive most of their flow from the hepatic artery. Several clinical trials
have explored the feasibility and the efficacy of TACE with microsphere as a treatment for
patients with colorectal liver metastasis. HepaSphere represents a novel drug delivery system
for chemoembolization, which can add two benefits to embolization therapy. First, by
ionically binding the doxorubicin throughout the microspheres, more drug can be delivered
into the tumor, with less escape into peripheral circulation. Second, conformability to the
architecture of the vessel lumen, providing more contact surface area with the embolic
material and the vessel intima, leading to a more complete occlusion. However, there are
limited experiences in using HepaSphere TACE for colorectal liver metastasis in Taiwan. In
this pilot study, we will evaluate the initiate safety and efficacy of Hepasphere
microspheres loaded with a chemotherapeutic agent doxorubicin for the treatment of patients
who have failed first-line and second-line systemic chemotherapy.
This is an open-label, non-comparative study aimed to evaluate the safety profiles and
efficacy of patients with unresectable colorectal liver metastases treated by selective TACE
(transarterial chemoembolization) using HepaSphere load with doxorubicin. Total of 15
patients will be planned to recruit.
The study procedures will consist of a screening period in which patient eligibility will be
determined. Patients meeting the study entry criteria will receive one HepaSphere treatments.
Computed tomography (CT) will be done 4 weeks after treatment to determine tumor response.
Hepatic progression free survival will be followed from the date of first study HepaSphere
procedure until a date of target liver tumor progression is obtained or the patient is lost
to follow-up. Treatments for liver metastases after the study HepaSphere treatments are
complete will be documented during the survival period to the extent possible.
The investigators will evaluate subjects' previous treatments and response, and determine to
use doxorubicin for subjects. 100 mg doxorubicin will be loaded onto the HepaSphere
Microspheres (through ionic bonding when the spheres are exposed to doxorubicin solubilized
in non-ionic contrast medium) and delivered via microcatheter. No ethiodized oil is used with
the microspheres. The occlusion endpoint will be stasis to the second or third branches. If
stasis has not been reached when the target dosage of doxorubicin has been delivered,
additional bland embolic agent will be used to achieve a consistent endpoint. Other
concurrent chemotherapy, such as Xeloda, 5-fluorouracil but not limited, can be used in
combination with HepaSphere Tx.
The study will evaluate safety throughout the protocol specified treatment phase of the
investigation by assessing adverse events, as well as changes from baseline in laboratory
values, findings on physical examination including vital signs and Eastern Cooperative
Oncology Group (ECOG) performance status. Concomitant medication usage will also be assessed.
;