Humanitarian Device Exemption (HDE) Treatment Protocol

Objectives:

There are no hypotheses to be tested in this treatment protocol which has the following objectives:

• Provide oversight to treatment with TheraSphere to eligible patients with hepatocellular carcinoma (HCC) of the liver who are not surgical resection candidates.
• Evaluate patient experience, toxicities and overall survival associated with TheraSphere treatment.

TheraSphere is a medical device containing yttrium-90 (Y-90), a radioactive material that has been used to treat liver tumors. When Y-90 is put into microscopic glass beads, called microspheres, it can be injected directly into the liver by vein. This allows a large dose of radiation to be delivered directly to the tumor, which lowers the risk of experiencing toxic radiation side effects from the radiation to in other parts of the body, or to healthy liver tissue. The radiation from TheraSphere treatment stays in the body and begins to lose its effect within 12 days, due to physical decay (please refer to the package insert for more information for more information regarding this). The glass microspheres will stay in the body from that point on, but should not cause any health problems.

All visits and procedures related to the TheraSphere treatment will be performed on an outpatient basis. About 2 weeks before the treatment begins, a small tube (catheter) will be inserted into a vein that goes to the liver, usually in the thigh.

TheraSphere Treatment:

TheraSphere (microspheres filled with Y-90 as described above) will be injected into the tumor in the liver through a catheter that you have already had placed into an artery during an earlier procedure.

You will receive at least 1 TheraSphere injection while you are receiving the treatment. If the doctor thinks it is needed, you will have a second injection about 1 month later. The number of TheraSphere injections you will receive will depend on the size and location of the tumors. The injection should take about 5 minutes to complete each time.

After receiving the TheraSphere injection, you will stay at the hospital for several hours so that the staff can check you for possible side effects. If you experience any serious problems or complications after receiving the injection, you may be admitted to the hospital for observation and possible additional treatment.

Length of Treatment:

You will continue to receive the HUD treatment indefinitely.

TheraSphere is a humanitarian use device that is approved by the FDA for the treatment of rare disorders affecting less than 4,000 people in the U.S. each year.

All of the tests and procedures that will be performed as part of this treatment protocol are considered to be standard care, including the TheraSphere.

Up to 200 patients will receive the treatment. All will be enrolled at M.D. Anderson.

• Carcinoma, Hepatocellular
• Liver Cancer

Inclusion Criteria:

1. Diagnosis of unresectable intrahepatic HCC. The histopathology confirmation criterion may be waived in patients with a radiographically identifiable liver mass, known laboratory or clinical risk factors for cancer or elevated tumor markers such as alphafetoprotein (AFP)^21 and clinical findings. Guidelines from the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) describe in detail the approach and algorithm for diagnosing HCC.
2. Eastern Cooperative Oncology Group (ECOG) Performance Status Score 0 - 1
3. Life expectancy >/= 3 months
4. > 4 weeks since prior radiation, surgery or chemotherapy
5. Able to comprehend and provide written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

1. Any pre-treatment laboratory findings within 15 days of treatment demonstrating liver dysfunction: • AST (Serum Glutamic-Oxalacetic Transaminase - SGOT) or ALT (Serum Glutamic-Pyruvic Transaminase - SGPT) > 5 times Upper Normal Limit (UNL) • Serum bilirubin > 2.0 mg/dl (unless segmental infusion is planned)
2. Any contraindications to angiography and hepatic artery catheterization such as: History of severe allergy or intolerance to any contrast media, narcotics, sedatives, or atropine that cannot be corrected or premedicated; Bleeding diathesis, not correctable by usual forms of therapy; Severe peripheral vascular disease that would preclude catheterization.
3. Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs in a single treatment
4. Clinical evidence of pulmonary insufficiency
5. Evidence of any detectable Technetium-99 Macroaggregated Albumin (Tc-99m MAA) flow to the stomach or duodenum, after application of established angiographic techniques to stop or mitigate such flow.
6. Complete occlusion of the main portal vein.
7. Significant extrahepatic disease representing an imminent life-threatening outcome
8. Active uncontrolled infection.
9. Significant underlying medical or psychiatric illness.
10. Co-morbid disease of condition that would preclude safe delivery of TheraSphere treatment or, in the judgment of the physician, place the patient at undue risk
11. Pregnancy
12. Tumor type demonstrated on imaging to be infiltrative, tumor volume > 70% of the target liver volume, or tumor nodules too numerous to count, or tumor volume > 50% combined with an albumin < 3 g/dL, or complete occlusion of the main portal vein.