A Phase II Study of Temsirolimus as Second-line Therapy in Patients With Advanced, Unresectable Hepatocellular Carcinoma

Inclusion Criteria:

1. Patients must have advanced unresectable or metastatic hepatocellular carcinoma
(HCC). Prior diagnosis of HCC could have been established histologically or based on
one of the following criteria:

- Liver mass > 2cm: Characteristic enhancement on at least one imaging
technique(triphasic CT scan, MRI, or contrast enhanced ultrasound) or AFP > 200
ng/ml.

- Liver mass between 1 and 2 cm: Characteristic enhancement on two imaging
techniques.Diagnosis of HCC must have been confirmed by biopsy if
non-characteristic enhancement on imaging.

2. All patients must have received exactly one prior systemic therapy (cytotoxic
chemotherapy or targeted therapies) and must not be eligible for further locoregional
treatment modalities.

3. All patients must have measurable disease per RECIST criteria.

4. Patients with previous locoregional therapies, including but not limited to
radio-frequency ablation, cryoablation, percutaneous ethanol injection,
chemo-embolization, hepatic artery embolization, and hepatic artery infused FUDR,
stereotactic radiotherapy are eligible provided they have documented progression of
their disease or have measurable extrahepatic disease.

5. Patients must have an ECOG performance status of 0 - 2 (see Appendix B).

6. Patients must be greater than or equal to 18 years of age.

7. Patients with Child-Pugh class A (score of 5-6) or class B (score of 7-9) are
eligible.

8. Patients must have adequate organ function as defined by:

- AST, ALT and Alkaline phosphatase ≤ 5x upper limit of normal (ULN)

- Total Bilirubin < 2 mg/dl.

- Creatinine clearance ≥ 15ml/min & patients must not be dialysis dependent.

9. Patients must have adequate bone marrow function as defined by:

- Leukocytes ≥ 2000 / mm3 or absolute neutrophil count (ANC) ≥ 1000 / mm3

- Platelet count ≥ 75000 / mm3

10. Pregnant and nursing women will be excluded from this study. All patients of
reproductive potential must agree to use adequate birth control measures to be
eligible for study enrollment.

11. Prior palliative radiotherapy is permissible provided it has been completed at least
2 weeks prior to study entry and the patient has recovered from any radiation-related
side effects.

12. Patients must not be receiving any other investigational agents or other anti-cancer
therapies. At least 28 days must have elapsed since completion of previous systemic
therapy prior to study entry and the patient should have recovered from all
toxicities related to prior therapy.

13. Patients must not have a history of other malignancies that are active and require
therapy (other than non-melanoma skin cancers).

Exclusion Criteria:

1. Patients with prior treatment with any mTOR inhibitor are not eligible.

2. Patients with a history of an uncontrolled intercurrent illness including, but not
limited to, ongoing or active infection, symptomatic congestive heart failure,
unstable angina pectoris,cardiac arrhythmia, or psychiatric illness/social situations
that would limit compliance with study requirements are not eligible.

3. Patients taking cytochrome P450 enzyme-inducers or inhibitors are not eligible.

4. Patients with a known history of HIV infection are not eligible.

5. Patients with uncontrolled hyperlipidemia or hypercholesterolemia are not eligible
(fasting serum cholesterol > 350 mg/dL or fasting serum triglycerides > 400 mg/dL).

6. Patients with a known history or clinical evidence of CNS metastases are not
eligible.

7. Patients who, in the best judgment of the investigator, will not be able to comply
with the requirements of the protocol are not eligible.

8. Patients with Child-Pugh class C liver disease are not eligible.

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