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

A Phase III Clinical Trial Evaluating TheraSphere® in Patients With Metastatic Colorectal Carcinoma of the Liver Who Have Failed First Line Chemotherapy

The effectiveness and safety of TheraSphere will be evaluated in patients with colorectal cancer with metastases in the liver, who are scheduled to receive second line chemotherapy. All patients receive the standard of care chemotherapy with or without the addition of TheraSphere.

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 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 (eg. closure device)
• 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
• 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