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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Liver Cancer
• Intervention / Treatment: Drug: capecitabine; Radiation: yttrium Y 90 glass microspheres

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 Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwestern University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2009
• Primary Completion (ACTUAL): March 19, 2014
• Study Completion (ACTUAL): July 8, 2014

Study Registration Dates

• First Submitted: March 6, 2009
• First Submitted That Met QC Criteria: March 6, 2009
• First Posted (ESTIMATE): March 9, 2009

Study Record Updates

• Last Update Posted (ACTUAL): September 9, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: liver metastases; advanced adult primary liver cancer; adult primary cholangiocellular carcinoma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Cholangiocarcinoma; Liver Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Central Nervous System Stimulants; Appetite Stimulants; Capecitabine; Doxifluridine
• Other Study ID Numbers: NU 08I5; NU-08I5; STU00007062; NCI-2009-01122 (OTHER: NCI CTRP#)