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A Phase II Study of Yttrium-90 Radioactive Resin Microspheres in the Treatment of Colorectal Adenocarcinoma Metastatic to the Liver After Failure of First-Line Combination Chemotherapy

Phase 2
18 Years
Open (Enrolling)
Colorectal Neoplasms, Liver Neoplasms

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Trial Information

A Phase II Study of Yttrium-90 Radioactive Resin Microspheres in the Treatment of Colorectal Adenocarcinoma Metastatic to the Liver After Failure of First-Line Combination Chemotherapy

This is a phase II, single-arm study of Yttrium-90 (Y-90) radioactive resin microspheres in
the treatment of colorectal adenocarcinoma metastatic to the liver in patients who have had
progressive disease through first line combination chemotherapy or have otherwise failed
first line chemotherapy due to toxicity. Expected enrollment at UCSD is approximately 34

The dose of Yttrium-90 radioactive resin microspheres is calculated based on body surface
area (to estimate normal liver volume), percentage of total liver represented by the
targeted lobe, and percentage of the lobe that is occupied by tumor, corrected for
percentage lung shunt. The prescribed dose, calculated by the nuclear medicine physician,
will be delivered by the interventional radiologist using the standard delivery system with
frequent fluoroscopic monitoring to assure ante grade blood flow immediately after
treatment. Additional current standard practice includes obtaining a nuclear medicine scan
of the patient immediately after each therapeutic Yttrium-90 microspheres administration to
prove delivery of the agent to the targeted portion of the liver and absence of either
extra-hepatic Yttrium-90 delivery or free Yttrium-90.

Blood samples will be obtained one week after the first treatment with microspheres. If the
patient has bi-lobar disease and the results of lab tests meet protocol specified criteria,
the dose will be repeated in the initially-untreated lobe. If the lab tests do not meet
protocol specified criteria (i.e. study inclusion/exclusion criteria), the treatment will be
deferred for fourteen days and labs repeated. If they are then within parameters, the
patient will receive the second dose. If they are not within parameters, the patient will
proceed to chemotherapy.

Patients will remain off chemotherapy after their final microspheres treatment for a minimum
of three weeks. Second line treatment options include FDA approved anti-neoplastic agents
used in colorectal cancer metastatic to the liver with the exception of bevacizumab and
capecitabine, which has been less rigorously studied with relation to Yttrium-90 radioactive
microspheres and therefore will not be used. When patients are found to have progressive
disease while receiving second line chemotherapy, they will then undergo a comprehensive
clinical, laboratory, and imaging assessment and enter the follow-up phase in which they are
assessed every five to seven months until death or withdrawal of consent.

A contrast enhanced ultrasound (CEUS) will be performed pre microsphere treatment (within 14
days), post microsphere treatment (2 weeks, 4 weeks, 8 weeks and 12 weeks post the
microsphere treatment). If patients require two treatments with microspheres, they will be
evaluated 2, 4, 8 and 12 weeks post the second treatment.

Inclusion Criteria:

- Histologically confirmed colorectal carcinoma. Liver metastasis will be confirmed by
either PET scan or biopsy.

- Ability to understand and willingness to sign written informed consent

- Minimum of 18 years of age

- Liver dominant metastases measurable by CT or MRI and therefore amenable to serial
assessment using RECIST criteria

- Progressive disease of metastatic colorectal carcinoma on first line combination
chemotherapy with a FOLFOX based regimen (Folinic Acid, Oxaliplatin and
Fluorouracil)or failure of first line chemotherapy due to toxicity

- Candidate for second line chemotherapy with a FOLFIRI regimen (Folinic Acid,
Fluorouracil & Irinotecan). Per standard of care, second line chemotherapy will not
include Bevacizumab.

- Karnofsky Performance Score (KPS) of 70% or greater

- Life expectancy of greater than or equal to four months by investigator estimation

- Females with negative urine or serum pregnancy test

- Effective double barrier contraception for a minimum of two months following the
final infusion of microspheres

- Patients who are not candidates for transarterial chemoembolization (TACE), thermal
ablation or surgical resection

Exclusion Criteria:

- Dominant extra-hepatic disease including cerebral metastases or other extra-hepatic
metastases that are symptomatic

- Large volume ascites assessed by cross sectional CT imaging

- Any chemotherapy < 4 weeks prior to the first microsphere treatment

- Anticipated to need Avastin chemotherapy within eight weeks of day M1

- Absolute neutrophil count (ANC) < 1.5 x 109/L

- Platelets (PLT) < 60,000/mm3

- Hemoglobin (Hgb) < 9.0 gm/dL

- Prothrombin time (PT) or Partial Prothrombin time (PTT) > upper limit of normal (ULN)

- Serum Creatinine > 2.0 mg/dL

- Forced expiratory volume (FEV1) < 1L by baseline pulmonary function tests (ordered if
investigator judges it to be clinically indicated)

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 5 times upper
limits of normal (ULN) or total bilirubin > 2.0 mg/dL

- History of incompetent sphincter of oddi (e.g.: sphincterotomy, biliary-enteric
anastamosis, or percutaneous biliary drain)

- Severe hypoalbuminemia (albumin < 2.0 g/dL)

- Alkaline phosphatase > 2.5 times ULN

- Greater than 20% lung shunting (determined by the MAA - Tc 99 nuclear medicine lung
shunt scan)

- Pre assessment angiogram and MAA scan demonstrating any uncorrectable activity in the
stomach, bowel or pancreas

- Major surgery < 4 weeks prior to the first microsphere treatment

- Female who is pregnant or nursing

- Men and women of childbearing potential wishing to conceive < 2 months following the
completion of the microsphere portion of the study.

- Any investigational agent administered < 4 weeks prior to microsphere treatment

- A known history of hepatitis B or hepatitis C

- Known hypersensitivity to any component of microsphere infusion

- History of, or current coagulation or bleeding disorder

- History of significant hepatic cirrhosis, fibrosis or hemochromatosis

- History of malignancy, other than colorectal cancer, within five years of the start
of study participation, except in situ cervical or skin cancer

- Active severe infection or any other concurrent disease or medical conditions that
are likely to interfere with the study as judged by the investigator

- Prior treatment with radioactive microspheres or external beam radiation therapy to
the liver

- Prophylactic anticoagulation and nonsteroidal antiplatelet drugs are only a
contraindication, if the PT/PTT are above the ULN. Plavix (clopidogrel) will need to
be stopped 5 days prior to the hepatic-angiogram and the microsphere procedures, then
started the next day.

- History of right to left, bi-directional or transient right to left cardiac shunts,
worsening or clinically unstable congestive heart failure, acute myocardial
infarction or acute coronary syndromes serious ventricular arrhythmias or high risk
for arrhythmias due to prolongation of the QT interval, respiratory failure as
manifested by signs or symptoms of carbon dioxide retention or hypoxemia or severe
emphysema, pulmonary emboli or other conditions that causes pulmonary hypertension
due to compromised pulmonary arterial vasculature

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria using Computerized Tomography (CT) assessment of tumor(s) at 6 months since the diagnosis date of disease progression on first-line therapy.

Outcome Time Frame:

4 years

Safety Issue:


Principal Investigator

Tony Reid, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Diego


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

January 2014

Related Keywords:

  • Colorectal Neoplasms
  • Liver Neoplasms
  • liver
  • colorectal
  • metastasis
  • carcinoma
  • Yttrium-90
  • microspheres
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Neoplasms
  • Colorectal Neoplasms
  • Liver Neoplasms



UCSD Medical Center La Jolla, California  92093
Thornton Hospital La Jolla, California  92037
The Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093