Efficacy Evaluation of TheraSphere Following Failed First Line Chemotherapy in Metastatic Colorectal Cancer

Inclusion Criteria

- Must be male or female, 18 years of age or older, and of any ethnic or racial group

- If primary tumor has not been resected, it must be clinically stable

- Must have colorectal cancer with unresectable metastatic disease to the liver
(unresectable unilobar or bilobar disease) who have disease progression in the liver
with oxaliplatin or irinotecan based first line chemotherapy

- Must be eligible to receive second-line standard-of-care chemotherapy with either 1)
an oxaliplatin-based chemotherapy regimen, or 2) an irinotecan-based chemotherapy
regimen

- Must have baseline efficacy images with measurable target tumors in the liver
according to RECIST 1.1 using standard imaging techniques taken within 28 days prior
to randomization. Images must be taken after, or at the time of completion of first
line chemotherapy

- Tumor replacement <50% of total liver volume

- Current Eastern Cooperative Oncology Group (ECOG) of 0-1 through screening to first
treatment on study

- Will have completed the first line chemotherapy regimen completed at least 14 days
prior to initiation of 2nd line chemotherapy under the protocol

- Patient is willing to participate in the study and has signed the study informed
consent

- Serum creatinine ≤ 2.0 mg/dL

- Serum bilirubin up to 1.2 x upper limit of normal

- Albumin ≥ 3.0 g/dL

- Must have neutrophil count >1200/mm3 (1.2x109/L)

Exclusion Criteria

- History of hepatic encephalopathy

- Contraindications to angiography and selective visceral catheterization such as
bleeding diathesis or coagulopathy that is not correctable by usual therapy of
hemostatic agents

- History of severe peripheral allergy or intolerance to contrast agents, narcotics,
sedatives or atropine that cannot be managed medically

- Presentation of pulmonary insufficiency or clinically evident chronic obstructive
pulmonary disease

- Cirrhosis or portal hypertension

- Prior external beam radiation treatment to the liver

- Prior intra-arterial liver directed therapy, including transcatheter arterial
chemoembolization (TACE) or Y-90 microsphere therapy

- Planned treatment with biological agents within 28 days prior to receiving TheraSphere
(may resume after Y-90 treatment or immediately if in control arm)

- Planned liver directed therapy or radiation therapy

- Intervention for, or compromise of, the Ampulla of Vater

- Clinically evident ascites (trace ascites on imaging is acceptable)

- Toxicities due to prior cancer therapy that have not resolved before the initiation of
study treatment, if the Investigator determines that the continuing complication will
compromise the safe treatment of the patient

- Significant life-threatening extra-hepatic disease, including patients who are on
dialysis, have unresolved diarrhea, have serious unresolved infections including
patients who are known to be human immunodeficiency virus (HIV) positive or have acute
hepatitis B virus (HBV) or hepatitis C virus (HCV)

- confirmed extra-hepatic metastases. Limited indeterminate extra-hepatic lesions in the
lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each
individual lesion <1 cm; any number of lymph nodes with each individual nodes <1.5 cm)

- Contraindications to the planned second line standard-of-care chemotherapy regimen

- Women of childbearing potential must have a negative serum pregnancy test within 14
days prior to randomization, and must not be breastfeeding and must agree to use
contraceptive for duration of study.

- Participation in a clinical trial with an investigational therapy within 30 days prior
to randomization

- Co-morbid disease or condition that would place the patient at undue risk and preclude
safe use of TheraSphere treatment, in the Investigator's judgment