Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas

Outline: This is a multi-center study.

Patients who meet eligibility criteria will receive treatment as follows until disease
progression or excessive toxicities:

- Erlotinib 150 mg p.o. daily on days 2-7, 9-14, 16-28

- Docetaxel 30 mg/m2 IV over 30 min weekly x 3 weeks on days 1, 8, 15

Treatment cycle = 28 days

Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

Life expectancy: At least 12 weeks

Hematopoietic:

- Absolute neutrophil count (ANC) > 1000 mm3

- Platelet count > 75,000 mm3

- Hemoglobin > 8 g/dL

Hepatic:

- Bilirubin < 2.0 x upper limit of normal (ULN)

- Transaminases (AST, ALT) < 5.0 x ULN if alkaline phosphatase is < 2.5 x ULN, or
alkaline phosphatase < 5 x ULN if transaminases are < 1.5 x ULN.

- If not on anticoagulation: PT < 4 seconds above ULN; INR < 1.5; PTT < 1.3 x ULN.

- If on therapeutic anticoagulation, patients may have an INR > 1.5 and PTT within
therapeutic range; INR will be monitored weekly until stable.

- Serum Albumin > 3.0

Renal:

- Creatinine clearance of > 60 ml/ min (by Cockcroft-Gault)

Pulmonary:

- Not specified

Inclusion Criteria:

- Histological or cytological proof of hepatocellular or biliary tract carcinomas, not
amenable to curative resection or transplantation.

- Prior cancer treatment completed at least 30 days prior to being registered for
protocol therapy and recovered from the acute toxicity effects of the regimen.

- Patients may have had radiofrequency ablation, cryosurgery or embolization, but must
have documented progressive disease with the involved lesion, or at least one
previously untreated lesion.

- Patients may have had ≤ 2 prior chemotherapy regimens.

- Prior radiation therapy allowed to < 25% of the bone marrow at least 30 days prior to
being registered for protocol therapy.

- Patients with biliary obstruction must have percutaneous transhepatic drainage or
endoscopic stent placement prior to starting study treatment.

- Patients with a history of malignancy are eligible provided they have been curatively
treated and demonstrate no evidence for recurrence of that cancer.

- Peripheral neuropathy ≤ grade 1.

- Patients must agree to abstain from frozen or fresh grapefruit or grapefruit juice
for 5 days prior to, and during treatment.

- Patients must be willing to use an effective method of contraception (hormonal or
barrier method of birth control; abstinence) while on treatment and for a 12 week
period thereafter.

- Females of childbearing potential must have a negative pregnancy test within 7 days
prior to being registered for protocol therapy.

- Written informed consent and HIPAA authorization for release of personal health
information.

- Age ≥ 18 years at time of consent.

Exclusion Criteria:

- No previous treatment with EGFR inhibitors.

- No treatment with any investigational agent within 30 days prior to being registered
for protocol therapy.

- No symptomatic brain metastasis. A subject with prior brain metastasis may be
considered if they have completed their treatment for brain metastasis, no longer
require corticosteroids, and are asymptomatic.

- No Child-Pugh B or C liver cirrhosis.

- No active corneal erosions or history of abnormal corneal sensitivity test.

- No history of aneurysm or arteriovenous malformation.

- No hemorrhage/bleeding event > CTCAE Grade 3 within 30 days prior to begin registered
for protocol therapy.

- No clinically significant infections as judged by the treating investigator.

- No condition that impairs patient's ability to swallow whole pills.

- No history of hypersensitivity to docetaxel or other drugs formulated with
polysorbate 80.

- Females must not be breastfeeding.

- Patients who cannot avoid the following medications will be ineligible for the trial:
midazolam, anti-mycotic agents (ketoconazole and related compounds), macrolide
antibiotics (erythromycin and related compounds), nifedipine, phenobarbital,
phenytoin, carbamazepine, and rifampin (induction) and anti-retrovirals (including
ritonavir, saquinavir).