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

Official Title: “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.

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.

Intervention(s) in this Clinical Trial

• 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
• Radiation: yttrium Y 90 resin microspheres
  • radiation

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Sir-Spheres

Primary Measures

• Symptomatic relief as measured by Carcinoid Symptom Scale, SF-36 Pain scale, and SF-36 physical component summary
  • Time Frame: Patients will be followed for at least one year (or until intervening death)
    Safety Issue?: No
• Toxicity as measured by CTC v3.0
  • Time Frame: Patients will be followed for at least one year (or until intervening death)
    Safety Issue?: Yes
• Disease progression
  • Time Frame: Patients will be followed for at least one year (or until intervening death)
    Safety Issue?: No
• Health-related quality of life
  • Time Frame: Patients will be followed for at least one year (or until intervening death)
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Vanderbilt-Ingram Cancer Center Other

Overall Clinical Trial Officials and Contacts

Steven G. Meranze, MD Principal Investigator Vanderbilt-Ingram Cancer Center  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00466856

Study ID Number: VICC GI0365

ClinicalTrials.gov Identifier: NCT00466856

Health Authority: United States: Food and Drug Administration

Clinical trial summary from the National Cancer Institute's PDQ® database