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

Northwestern University

Status and phase: Completed; Phase 1

Conditions: Metastatic Cancer; Liver Cancer

Treatments: Drug: capecitabine; Radiation: yttrium Y 90 glass microspheres

Study type: Interventional

Funder types: Other

Identifiers

NCT00858429

NCI-2009-01122 (Other Identifier)

NU 08I5

NU-08I5

STU00007062

Details and patient eligibility

About

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.

Full 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.

Enrollment: 18 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 4 patient groups

Cohort 1 (capecitabine, Y90)

Experimental group

Description:

2,000mg/m2 capecitabine +110 Y90

Treatment:

Radiation: yttrium Y 90 glass microspheres

Drug: capecitabine

Cohort 2 (capecitabine , Y90)

Experimental group

Description:

2,000mg/m2 capecitabine + 130 Y90

Treatment:

Radiation: yttrium Y 90 glass microspheres

Drug: capecitabine

Cohort 3 (capecitabine, Y90)

Experimental group

Description:

2,000mg/m2 Capecitabine + 150 Y90

Treatment:

Radiation: yttrium Y 90 glass microspheres

Drug: capecitabine

Cohort 4 (capecitabine, Y90)

Experimental group

Description:

2,000 mg/m2 capecitabine = 170 Y90

Treatment:

Radiation: yttrium Y 90 glass microspheres

Drug: capecitabine