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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Liver Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: capecitabine
* Radiation: yttrium Y 90 glass microspheres


Participation Criteria
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Eligibility Criteria
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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 PRIOR CONCURRENT THERAPY: No prior radiotherapy to the liver No more than 2 prior therapies for metastatic disease to the liver No prior intervention to or compromise of the Ampulla of Vater At least 4 weeks since prior and no concurrent sorivudine or brivudine No concurrent cimetidine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (capecitabine, Y90)<br>2,000mg/m2 capecitabine +110 Y90 | Drug: capecitabine<br>* 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3.<br>* Other names: prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR);Radiation: yttrium Y 90 glass microspheres<br>* 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.<br>|
| Experimental: Cohort 2 (capecitabine , Y90)<br>2,000mg/m2 capecitabine + 130 Y90 | Drug: capecitabine<br>* 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3.<br>* Other names: prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR);Radiation: yttrium Y 90 glass microspheres<br>* 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.<br>|
| Experimental: Cohort 3 (capecitabine, Y90)<br>2,000mg/m2 Capecitabine + 150 Y90 | Drug: capecitabine<br>* 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3.<br>* Other names: prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR);Radiation: yttrium Y 90 glass microspheres<br>* 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.<br>|
| Experimental: Cohort 4 (capecitabine, Y90)<br>2,000 mg/m2 capecitabine = 170 Y90 | Drug: capecitabine<br>* 1000 mg/m2 twice daily, for 14 consecutive days followed by a 7 day treatment free rest period for cycles 1, 2 and 3.<br>* Other names: prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR);Radiation: yttrium Y 90 glass microspheres<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced adult primary liver cancer, liver metastases, adult primary cholangiocellular carcinoma