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

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

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.

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer; Metastatic Cancer; Pheochromocytoma; Islet Cell Tumor
• Intervention / Treatment: Drug: octreotide acetate; Radiation: yttrium Y 90 resin microspheres

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232-6838
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sir-Spheres	Drug: octreotide acetate; 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; Other Names: octreotide; Radiation: yttrium Y 90 resin microspheres; radiation; Other Names: octreotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (ACTUAL): October 1, 2006
• Study Completion (ACTUAL): October 1, 2007

Study Registration Dates

• First Submitted: April 25, 2007
• First Submitted That Met QC Criteria: April 25, 2007
• First Posted (ESTIMATE): April 27, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: liver metastases; metastatic gastrointestinal carcinoid tumor; recurrent gastrointestinal carcinoid tumor; thyroid gland medullary carcinoma; metastatic pheochromocytoma; recurrent pheochromocytoma; gastrinoma; insulinoma; WDHA syndrome; glucagonoma; pancreatic polypeptide tumor; somatostatinoma; recurrent islet cell carcinoma; neoplastic syndrome
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neoplastic Processes; Pancreatic Diseases; Adenoma; Pancreatic Neoplasms; Paraganglioma; Neoplasm Metastasis; Neuroendocrine Tumors; Adenoma, Islet Cell; Pheochromocytoma; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: VICC GI 0365; VU-VICC-GI-0365