Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers

The incidence and mortality of HCC has increased in the United States. Promising responses
have been observed in HCC patients treated with gemcitabine and cisplatin, inclusing good
disease stabilization and progression free survival. Cisplatin-gemcitabine enhances the
cytotoxicity of cisplatin by increasing the formation of cytotoxic platinum DNA adducts.
Similarly, Oxaliplatin also has DNA cross linkage properties and one could assume that its
combination with gemcitabine is likely to potentiate the cytotoxicity of the latter.
Erlotinib has also been reported to result in clinical benefit in HCC and BTC patients. Based
on these prior findings, we embarked on this phase II protocol of gemcitabine, oxaliplatin,
and erlotinib in HCC and BTC patients.

Inclusion Criteria:

- Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or biliary
tree cancer (BTC:: intra- and extra-hepatic cholanciocarcinoma, bile duct cancer,
adenocarcinoma of the Ampulla of Vater and/or gallbladder carcinoma).

- Patients must have measurable disease according to Response Evaluation Criteria in
Solid Tumors (RECIST).

- Age 18 years or older.

- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2

- Adequate bone marrow as evidenced by:

- Absolute neutrophil count (ANC) > 1,500/L.

- Platelet count > 100,000/L.

- Absence of a regular red blood cell transfusion requirement.

- Adequate renal function as evidenced by serum creatinine < 1.5 mg/dL.

- Adequate hepatic function as evidenced by:

- Serum total bilirubin 1.5x Upper Limit of Normal (ULN).

- Alkaline phosphatase < 3x ULN for the reference lab (< 5x ULN for patients with
known hepatic metastases).

- Serum glutamic-oxaloacetic transaminase (SGOT)/ serum glutamic-pyruvic
transaminase (SGPT) < 3x ULN for the reference lab (< 5x ULN for patients with
known hepatic metastases).

- Patients must have a life expectancy of 12 weeks.

- Patients must be recovered from both acute and late effects of any prior surgery,
radiotherapy or other antineoplastic therapy.

- Patients of childbearing potential agree to use an effective form of contraception
during the study and for 90 days following the last dose of study medication (an
effective form of contraception is an oral contraceptive or a double barrier method).

Exclusion Criteria:

A patient may not be enrolled in the trial if any of the following criteria are met:

- Patients with an active infection or with a fever > 38.50 degrees Celcius within 3
days of the first scheduled day of protocol treatment.

- Patients with active central nervous system (CNS) metastases. Patients with stable CNS
disease, who have undergone radiotherapy at least 4 weeks prior to the planned first
protocol treatment and who have been on a stable dose of corticosteroids for 3 weeks
are eligible for the trial.

- History of prior malignancy within the past 5 years except for curatively treated
basal cell carcinoma of the skin, cervical intra-epithelial neoplasia, or localized
prostate cancer with a current prostate serum antigen (PSA) of < 1.0 mg/dL on 2
successive evaluations at least 3 months apart, with the most recent evaluation within
4 weeks of entry.

- Patients with prior treatment or known hypersensitivity to any of the components of
oxaliplatin or gemcitabine.

- Patients who have received chemotherapy within 30 days of the first scheduled day of
protocol treatment.

- Patients who received radiotherapy to more than 25% of their bone marrow; or patients
who received any radiotherapy within 4 weeks of entry.

- Patients who are receiving concurrent investigational therapy or who have received
investigational therapy within 30 days of the first scheduled day of protocol
treatment (investigational therapy is defined as treatment for which there is
currently no regulatory authority approved indication).

- Peripheral neuropathy Grade 2.

- Patients who are pregnant or lactating.

- Patients with a life expectancy of less than 12 weeks.

- Any other medical condition, including mental illness or substance abuse, deemed by
the Investigator, likely to interfere with a patient's ability to sign informed
consent, cooperate and participate in the study, or interfere with the interpretation
of the results.

- Patients with any of the following laboratory parameters:

- Abnormal hematological values with ANC < 1500/mm3, thrombocytopenia < 99,000.

- Impaired renal function with a serum creatinine > 1.5x ULN.

- Serum bilirubin > 1.5xULN.

- Albumin < 2.5 mg/dl.

- Unwillingness to participate or inability to comply with the protocol for the duration
of the study.

- History of allogeneic transplant.

- Known human immunodeficiency virus (HIV).

- Clinically significant heart disease defined as New York Heart Association (NYHA)
class 3 or 4 heart disease.

- Known or existing uncontrolled coagulopathy.

- Patients with severe medical problems such as uncontrolled diabetes or chronically
debilitating diseases that the investigator feels might compromise the study
participant.