Inclusion Criteria:

- Histologic Diagnosis: Patients must have a histologically or cytologically proven
hepatocellular cancer (HCC) that is not amenable to treatment via resection or liver
transplantation. In the absence of a tissue diagnosis, nodules on CT with a
characteristic appearance of HCC plus Alpha Fetoprotein (AFP) > 400ng/ml will be
considered diagnostic of HCC.

- Measurable Disease: Patients must have measurable disease.

Measurable lesions are defined as those that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥20 mm with conventional techniques (PET,
CT, MRI, x-ray) or as ≥10 mm with spiral CT scan. All tumor measurements must be recorded
in millimeters (or decimal fractions of centimeters).

A positive bone scan, osteoblastic metastases, and pleural or peritoneal effusions are not
considered measurable. Patients with only these lesions are not eligible for entry to the
study.

- Prior Therapy: Patients may or may not have received prior systemic therapy in the
metastatic setting. No prior treatment with an mTOR inhibitor or with doxorubicin is
permitted. Participants must have recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study. No
chemotherapy or radiotherapy may be given within 4 weeks prior to the start of
protocol treatment.

- Age: Patients must be ≥18 years old. Because no dosing or toxicity data are
currently available on the use of temsirolimus in combination with pegylated
liposomal doxorubicin in patients <18 years of age, children are excluded from this
study.

- Performance Status: ECOG 0-2 at study entry.

- Life Expectancy: Patients must have a life expectancy of greater than 12 weeks.

Required Laboratory Values:

- absolute neutrophil count ≥1,500/mm3

- platelets ≥100,000/mm3

- hemoglobin ≥9.0 g/dL

- total bilirubin ≤1.5 x ULN

- AST(SGOT)/ALT(SGPT) ≤1.5 x ULN (≤2.5 x ULN for patients with liver metastases)

- alkaline phosphatase ≤2.5 x ULN

- creatinine ≤1.5 x ULN OR

- creatinine clearance ≥60 mL/min/1.732 for patients with creatinine levels
above 2.0 mg/dl

- serum cholesterol ≤350 mg/dL /9.0 mmol/L (fasting)

- triglycerides ≤400 mg/dL (fasting)*

- albumin ≥3.0 mg/dL

- Patients with triglyceride levels >400 mg/dL can be started on lipid lowering
agents and reevaluated within 1 week. If levels go to ≤400 mg/dL, they can be
considered for the trial and continue the lipid lowering agents.

- Child-Pugh (CP) A or B liver dysfunction are eligible unless the bilirubin is
>1.5 x ULN. If non-contraindicated, hepatic impairment (bilirubin >1-1.5 x ULN
or AST >ULN but bilirubin ≤ULN) is present patients can be treated at a lower
dose (15 mg/week) of temsirolimus.

- Concomitant Medications: Temsirolimus is primarily metabolized by CYP3A4. Patients
cannot be receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin,
carbamazepine, phenobarbital) nor any other CYP3A4 inducer such as rifampin or St.
John's wort, as these may decrease temsirolimus levels. A partial list of agents
which interact with cytochrome P450 (CYP3A) is found in Appendix B. Use of agents
that potently inhibit CYP3A (and hence may raise temsirolimus levels), such as
ketoconazole, is discouraged, but not specifically prohibited. Temsirolimus can
inhibit CYP2D6, and may decrease metabolism (and increase drug levels) of drugs that
are substrates for CYP2D6, such as codeine. The appropriateness of use of such agents
is left to physician discretion. A list of drugs that may have potential interactions
with CYP2D6 is found in Appendix A. If there is any doubt about eligibility based on
concomitant medication, the Principal Investigator should be contacted. All
concomitant medications must be recorded.

- Known Allergies: Patients with known hypersensitivity reactions to macrolide
antibiotics (such as erythromycin, clarithromycin, and azithromycin) are not eligible
for this trial.

- Cardiac Function: Patients must have a normal left ventricular ejection fraction
(LVEF ≥50%) by MUGA scan.

- Sexually Active Patients: For all sexually active patients, the use of adequate
contraception (hormonal or barrier method of birth control) will be required prior to
study entry and for the duration of study participation. Non-pregnant status will be
determined in all women of childbearing potential. Pregnant and nursing women are
not eligible.

- HIV-Positive Patients: Patients receiving anti-retroviral therapy (HAART) for HIV
infection are excluded from the study because of possible pharmacokinetic
interactions. Appropriate studies will be undertaken in patients receiving HAART
therapy, when indicated.

- Neurologic Status: Patients must not have active CNS disease.

- Recovery from Intercurrent Illness: Patients must have recovered from uncontrolled
intercurrent illness including, but not limited to, ongoing or active infection,
symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.

- Informed Consent: Patients must have signed a Washington University Human Research
Protection Office (HRPO) approved informed consent. The patient should not have any
serious medical or psychiatric illness that would prevent either the giving of
informed consent or the receipt of treatment.

- Inclusion of Women and Minorities: Entry to this study is open to both men and women
and to all racial and ethnic subgroups.