Clinical trial NCT01253148: Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres for Cholangiocarcinoma
Official title: Phase II Study Of Intrahepatic Arterial Injection of 90-Y Glass Microspheres As First-Line Treatment For Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cholangiocarcinoma
Keywords: Liver
Bile Duct
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: BTG International Inc.
First posted: 2010-12-03
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if Therasphere will be a better way to treat cholangiocarcinoma. The investigators want to find out what effects, good and/or bad, this treatment will have on the patient and their cancer.

Detailed description: The goal of treatment with TheraSphere is to allow a large dose of radiation to be delivered directly to the tumor with less risk of toxic effects from radiation to other parts of the body or to healthy liver tissue when compared with currently available treatments.

The standard treatment for cholangiocarcinoma is surgery (if possible), external beam radiation therapy and/or chemotherapy. External beam radiation therapy to the liver may reduce symptoms, but only 20% of patients experience significant tumor shrinkage. Chemotherapy has response rates ranging from 6-19%. More recently, a new approach has been developed, called TheraSphere. Based on the results of earlier studies with TheraSphere, the study doctors at Moffitt feel this is a reasonable alternative to the standard treatment for this disease.

TheraSphere has restricted approval from the United States Food and Drug Administration (FDA) for the treatment of hepatocellular liver cancer; but it has not yet been approved for the treatment of cholangiocarcinoma. TheraSphere is a medical device containing yttrium-90 (Y-90), a radioactive material that has been used previously in the treatment of liver tumors. Y-90 is incorporated into very tiny glass beads called microspheres and is injected into the liver through the blood vessels supplying the liver.

Eligibility criteria: Inclusion Criteria:

* Patients must have newly diagnosed or recurrent (post surgery) histologically or cytologically proven cholangiocarcinoma.
* Patients can have solitary, multifocal unilobar, or bilobar disease without evidence of extrahepatic involvement. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>10 mm with spiral computed tomography (CT) scan or magnetic resonance imaging (MRI).
* Age \>18 years
* Life expectancy of greater than 3 months based on physician judgment
* Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2 (Karnofsky 50%)
* No prior chemotherapy or radiation treatment for cholangiocarcinoma
* Childs-Pugh score A or Childs-Pugh score B without portal vein thrombus
* Lung shunting that predicts lung dose to be \<30 Gy in a single treatment
* The effects of TheraSpheres on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because radioactive spheres are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
* Ability to understand and the willingness to sign a written informed consent document
* Adequate baseline hematopoietic function:

  * total white blood cell count equal to or greater than 3,000/mm³
  * absolute granulocyte count greater than 1,500/mm³
  * platelet count equal to or greater than 100,000/mm³
  * Hemoglobin \>8.0

Exclusion Criteria:

* Patients receiving any other investigational agents
* Patients with extrahepatic disease
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because TheraSpheres are radioactive and radiation is a known agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with TheraSpheres, breastfeeding should be discontinued if the mother is treated with TheraSpheres.
* Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy. In addition, antiretrovirals are known radiation sensitizers and could dramatically increase the risk of fulminant hepatic failure. Therefore, HIV-positive patients are excluded from the study because of possible lethal side effects.
* Bulk disease (tumor volume \> 70% of the target liver volume, or tumor nodules too numerous to count)
* Aspartic transaminase (AST) or alanine transaminase (ALT) \> 5 times upper limit of normal (ULN)
* Bilirubin \> 2 mg/dL
* Child-Pugh C Liver Cirrhosis
* Tumor volume \> 50% combined with an albumin \< 3 g/dL
* Complete occlusion of main portal vein causing portal hypertension

Primary outcomes:
measure: Median Progression Free Survival (PFS)
timeFrame: End of post treatment follow-up period of 20 months
Secondary outcomes:
measure: Median Overall Survival (OS)
timeFrame: Up to 36 months
measure: Overall Response Rate (ORR)
timeFrame: End of post treatment follow-up period of up to 20 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Sarah Hoffe, M.D.
role: PRINCIPAL_INVESTIGATOR
References: