Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer
Erlotinib in Treating Patients With Unresectable Liver, Bile Duct, or Gallbladder Cancer
Phase II trial to study the effectiveness of erlotinib in treating patients who have
 unresectable liver, bile duct, or gallbladder cancer. Biological therapies such as erlotinib
 may interfere with the growth of cancer cells and slow the growth of the tumor.
PRIMARY OBJECTIVES:

 I. To evaluate the proportion of patients with unresectable hepatocellular or biliary
 carcinoma treated with OSI-774 who are progression-free at 24 weeks.

 SECONDARY OBJECTIVES:

 I. To evaluate the toxicity profile of this treatment in each of the patient groups.

 II. To evaluate the objective response rate of patients with hepatocellular or biliary
 carcinoma treated with OSI-774.

 III. To evaluate overall and progression-free survival. IV. To assess the EGFR protein levels
 and explore their association with clinical outcome.

 OUTLINE: This is a multicenter study. Patients are assigned to 1 of 2 groups according to
 cancer type (hepatocellular vs biliary).

 Patients receive oral erlotinib once daily. Treatment repeats every 28 days for at least 6
 courses in the absence of disease progression or unacceptable toxicity.

 Patients are followed every 3 months for up to 3 years.
Inclusion Criteria:

 -  Histologically or cytologically confirmed hepatocellular carcinoma (HCC) or biliary
 carcinoma that is surgically unresectable; exception: for surgically unresectable HCC,
 a hypervascular mass on CT and an AFP > 100ng/mL will suffice as noninvasive
 diagnostic criteria

 -  Measurable disease defined as at least one lesion whose longest diameter can be
 accurately measured as ≥ 2.0 cm

 -  Absolute neutrophil count (ANC) ≥ 1500/mm3

 -  PLT ≥ 75,000/mm3

 -  Total bilirubin ≤ 2 x upper normal limits (UNL)

 -  Serum AST ≤ 3 x UNL

 -  Serum ALT ≤ 3 x UNL

 -  Serum creatinine ≤ 2 mg/dL

 -  Serum albumin ≥ 2.5 g/dL

 -  Patients not receiving anticoagulation: INR ≤ 1.5

 -  ECOG performance status (PS) 0, 1, or 2

 -  Estimated life expectancy ≥ 3 months

 -  Capable of understanding the investigational nature, potential risks and benefits of
 the study and able to provide written informed consent

 -  HCC Patients Only: Child-Pugh classification of A or B

 -  For patients having prior cryotherapy, radiofrequency ablation, ethanol injection, or
 photodynamic therapy, the following criteria must be met:

 -  > 6 weeks has elapsed since that therapy

 -  Indicator lesion(s) is/are outside the area of prior treatment or, if the only
 indicator lesion is inside the prior treatment area, there must be clear evidence
 of disease progression associated with that lesion

 -  Edges of the indicator lesion are clearly distinct on CT scanning

 Exclusion Criteria:

 -  Ampulla of Vater tumors

 -  Any of the following as this regimen may be harmful to a developing fetus or nursing
 child:

 -  Pregnant women

 -  Breastfeeding women

 -  Men or women of childbearing potential or their sexual partners who are unwilling
 to employ adequate contraception (condoms, diaphragm, birth control pills,
 injections, intrauterine device [IUD], surgical sterilization, subcutaneous
 implants, or abstinence, etc.)

 -  NOTE: The effects of OSI-774 on the developing human fetus at the recommended
 therapeutic dose are unknown

 -  Any of the following:

 -  > 1 prior systemic anticancer therapy; Note: Chemoembolization will be considered
 as one prior chemotherapeutic regimen.

 -  Prior EGFR targeting therapy

 -  Nitrosoureas or mitomycin C ≤6 weeks prior to study entry

 -  Other chemotherapy ≤4 weeks prior to study entry

 • Immunotherapy ≤ 4 weeks prior to study entry

 -  Biologic therapy ≤ 4 weeks prior to study entry

 -  Radiation therapy ≤ 4 weeks prior to study entry

 -  Prior cryotherapy, radiofrequency ablation, ethanol injection or photodynamic
 therapy ≤6 weeks prior to study entry

 -  Failure to fully recover from adverse effects of prior therapies regardless of
 interval since last treatment

 -  Other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy
 or supportive care considered investigational

 -  Major surgery, or significant traumatic injury occurring ≤ 3 weeks prior to
 planned treatment start date

 -  Any of the following:

 -  Gastrointestinal tract disease resulting in an inability to take oral medication

 -  Requirement for IV alimentation

 -  Prior procedures affecting absorption

 -  Active peptic ulcer disease

 -  History of other malignancy other than hepatocellular or biliary carcinoma within the
 previous 3 years, except for adequately treated basal cell or squamous cell skin
 cancer, or carcinoma of the cervix

 -  Known abnormalities of the cornea such as:

 -  History of dry eye syndrome or Sjorgen's syndrome

 -  Congenital abnormality (e.g., Fuch's dystrophy)

 -  Abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose)

 -  Abnormal corneal sensitivity test (Schirmer test or similar tear production test)

 -  Known CNS metastases; NOTE: These patients are excluded from this clinical trial
 because of their poor prognosis and because they often develop progressive neurologic
 dysfunction that would confound the evaluation of neurologic and other adverse events

 -  Uncontrolled intercurrent illness including, but not limited to:

 -  Ongoing or active infection

 -  Symptomatic congestive heart failure

 -  Unstable angina pectoris, cardiac arrhythmia

 -  Psychiatric illness/social situations that would limit compliance with study
 requirements

 -  HIV-positive patients receiving combination anti-retroviral therapy; NOTE: Patients
 with immune deficiency are at increased risk of lethal infections when treated with
 marrow-suppressive therapy; these patients are excluded from the study because of
 possible pharmacokinetic interactions with OSI-774; appropriate studies will be
 undertaken in patients receiving combination antiretroviral therapy when indicated