Yttrium Y 90 Glass Microspheres and Capecitabine in Treating Patients With Liver Cholangiocarcinoma or Liver Metastases

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT00858429

Collaborator

(none)

Enrollment

Location

Arms

63.2

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells. Specialized radiation therapy, such as yttrium Y 90 glass microspheres that deliver a high dose of radiation directly to the tumor, may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Capecitabine may also make tumor cells more sensitive to radiation therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of yttrium Y 90 glass microspheres when given together with capecitabine in treating patients with liver cholangiocarcinoma or liver metastases.

Condition or Disease	Intervention/Treatment	Phase
Liver Cancer Metastatic Cancer	Drug: capecitabine Radiation: yttrium Y 90 glass microspheres	Phase 1

Detailed Description

OBJECTIVES:

Establish the maximally tolerated dose of yttrium Y 90 glass microspheres in combination with capecitabine in patients with intrahepatic cholangiocarcinoma or liver metastases.
Characterize the toxicity of this regimen in these patients.
Determine the time to tumor progression in these patients.

OUTLINE: This is a dose escalation study of yttrium Y 90.

Patients receive oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Patients also receive yttrium Y 90 glass microspheres by intra-arterial hepatic infusion on days 1-7 of course 2.

After completion of study therapy, patients are followed every 3 months for 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Dose Escalating Study of Yttrium 90 Microspheres (TheraSphere) With Capecitabine (Xeloda) for Intrahepatic Cholangiocarcinoma or Metastatic Disease to the Liver

Actual Study Start Date :

Apr 1, 2009

Actual Primary Completion Date :

Mar 19, 2014

Actual Study Completion Date :

Jul 8, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 (capecitabine, Y90) 2,000mg/m2 capecitabine +110 Y90	Drug: capecitabine 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3. Other Names: C14H15FN3O7 prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) Radiation: yttrium Y 90 glass microspheres The amount of radioactivity required to deliver the desired dose to the liver is calculated using a formula. The dose depends on the cohort upon which the patient is enrolled. Y90 is administered during Cycle #2 on days 1-7.
Experimental: Cohort 2 (capecitabine , Y90) 2,000mg/m2 capecitabine + 130 Y90	Drug: capecitabine 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3. Other Names: C14H15FN3O7 prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) Radiation: yttrium Y 90 glass microspheres The amount of radioactivity required to deliver the desired dose to the liver is calculated using a formula. The dose depends on the cohort upon which the patient is enrolled. Y90 is administered during Cycle #2 on days 1-7.
Experimental: Cohort 3 (capecitabine, Y90) 2,000mg/m2 Capecitabine + 150 Y90	Drug: capecitabine 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3. Other Names: C14H15FN3O7 prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) Radiation: yttrium Y 90 glass microspheres The amount of radioactivity required to deliver the desired dose to the liver is calculated using a formula. The dose depends on the cohort upon which the patient is enrolled. Y90 is administered during Cycle #2 on days 1-7.
Experimental: Cohort 4 (capecitabine, Y90) 2,000 mg/m2 capecitabine = 170 Y90	Drug: capecitabine 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3. Other Names: C14H15FN3O7 prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) Radiation: yttrium Y 90 glass microspheres The amount of radioactivity required to deliver the desired dose to the liver is calculated using a formula. The dose depends on the cohort upon which the patient is enrolled. Y90 is administered during Cycle #2 on days 1-7.

Outcome Measures

Primary Outcome Measures

Maximal tolerated dose of yttrium Y 90 [During treatment and any time up to 6 weeks post-treatment]
Toxicity profile of yttrium Y 90 [During treatment and up to 30 days post-treatment]
Toxicity will be defined as number of adverse events related to treatment experienced during treatment
Time to tumor progression [At time of disease progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
Intrahepatic cholangiocarcinoma
Metastatic cancer confined to the liver
Measurable disease, defined as ≥ 1 lesion that can be accurately measured in ≥ 1 dimension as ≥ 20 mm by conventional techniques or as ≥ 10 mm by spiral CT scan
Must have tumor volume ≤ 50% of total liver volume based on visual estimation

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 75,000/mm^3
Serum creatinine ≤ 2.0 mg/dL
Serum bilirubin ≤ 1.5 times upper limit of normal
Albumin ≥ 2.0 g/dL
No baseline symptoms or laboratory values > grade 2 in severity by NCI CTCAE v 3.0 criteria
Not pregnant or nursing
Fertile patients must use effective contraception
No malabsorption syndrome
No severe liver dysfunction or pulmonary insufficiency
No complete occlusion of the main portal vein
No contraindication to iodine-based contrast agents
No contraindication to hepatic artery catheterization (e.g., vascular abnormalities or bleeding diathesis)
No prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to fluorouracil, or known dihydropyrimidine dehydrogenase deficiency