Internal Radiation Therapy in Treating Patients With Liver Metastases From Neuroendocrine Tumors

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. PURPOSE: This phase II trial is studying how well internal radiation therapy works in treating patients with liver metastases from neuroendocrine tumors.

Detailed Description
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OBJECTIVES: Primary Determine tumor response to selective internal radiation therapy with yttrium Y 90 resin microspheres (Sir-Spheres®) in patients with progressive liver metastases from neuroendocrine tumors. Secondary Determine the toxicity of this treatment in these patients. Determine the symptomatic relief of patients treated with this regimen. Determine the health-related quality of life of patients receiving this treatment. OUTLINE: Patients have an catheter placed into the hepatic artery percutaneously through the groin and then undergo selective internal radiation therapy with yttrium Y 90 resin microspheres (Sir-Spheres®) via the catheter on day 1. Patients also receive octreotide acetate IV 1 hour prior to, during, and 2 hours after Sir-Spheres® injection. Patients may undergo above treatment in another lobe of the liver (if each lobe is treated separately) 4 weeks later. Patients undergo functional performance, health-related quality of life, and symptom severity assessment prior to initial treatment and after completion of study treatment. After completion of study treatment, patients are followed periodically for at least 1 year. PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Official Title
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Clinical Trial of Sir-Spheres® in Patients With Symptomatic or Progressive Hepatic Metastases From Neuroendocrine Tumors

Conditions
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Head and Neck Cancer, Islet Cell Tumor, Metastatic Cancer, Pheochromocytoma

Intervention / Treatment
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* Drug: octreotide acetate
* Radiation: yttrium Y 90 resin microspheres


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed neuroendocrine tumor metastatic to the liver Well-differentiated or moderately well-differentiated neuroendocrine tumors Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm with conventional techniques or ≥ 10 mm with spiral CT scan Symptomatic disease, meeting one of the following criteria: Refractory carcinoid symptoms, defined as Carcinoid Symptom Severity scale > 2 despite use of octreotide acetate at ≥ 200 mcg subcutaneously three times daily (or 20 mg intramuscularly once monthly) for ≥ 4 weeks Evidence of radiographic progression with either of the following manifestations: Moderate-severe right upper quadrant pain and unintentional weight loss > 10% Decline in Karnofsky performance status > 10 points At least a 20% increase in the sum of the longest diameters of target lesions in the liver within the past 12 months No more than 75% replacement of normal liver by neuroendocrine tumor No more than 20% arteriovenous lung shunting on a technetium Tc 99m macro-aggregated albumin nuclear scan No equivocal, nonmeasurable, or nonevaluable liver metastasis PATIENT CHARACTERISTICS: Karnofsky performance status 50-100% Life expectancy ≥ 6 months Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Creatinine ≤ 1.5 mg/dL Bilirubin ≤ 2.0 mg/dL Albumin ≥ 3.0 g/dL Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 65,000/mm³ Hemoglobin > 9.0 g/dL INR ≤ 1.4 No hepatic arterial anatomy that would preclude the administration of study treatment into the liver No nonmalignant disease that would preclude study participation No other malignancy within the past 5 years except for cured basal cell carcinoma of the skin or cured carcinoma in situ of the uterine cervix PRIOR CONCURRENT THERAPY: Prior surgery, chemotherapy, or locally ablative technique for the liver cancer allowed No prior radiotherapy to the upper abdomen that includes the liver in the treatment field No investigational drug or agent/procedure (i.e., participation in another clinical trial) within the past 4 weeks No other specific anticancer treatment (other than octreotide acetate) during and for 3 months after completion of study therapy

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sir-Spheres<br> | Drug: octreotide acetate<br>* Lung/liver Ratio Dose of SIR-Spheres <10% Administer full dose of SIR-Spheres 10% to 15% Reduce dose of SIR-Spheres by 20% 16% to 20% Reduce dose of SIR-Spheres by 40% >20% Do not give SIR-Spheres<br>* Other names: octreotide;Radiation: yttrium Y 90 resin microspheres<br>* radiation<br>* Other names: octreotide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response |  | at 1 year or until intervening death | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as measured by CTC v3.0 |  | at 1 year or until intervening death | 
| Symptomatic relief as measured by Carcinoid Symptom Scale, SF-36 Pain scale, and SF-36 physical component summary | The Carcinoid Symptom Severity Scale is a self-report instrument that addresses the severity and frequency of symptoms and their impact on daily living. | at 1 year or until intervening death | 
| Patient report of Health-related quality of life (HRQOL) | HRQOL will be determined via the Medical Outcome Study 36-item short form, which includeds 8 individual scales, physical and mental component summary scores and is normed to both health and clinical populations. | at 1 year or until intervening death | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neoplastic syndrome, metastatic gastrointestinal carcinoid tumor, recurrent gastrointestinal carcinoid tumor, thyroid gland medullary carcinoma, metastatic pheochromocytoma, recurrent islet cell carcinoma, liver metastases, recurrent pheochromocytoma, gastrinoma, insulinoma, WDHA syndrome, glucagonoma, pancreatic polypeptide tumor, somatostatinoma