Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery
Condition: Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer
MeSH terms: Carcinoma, Hepatocellular; Liver Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Recurrence
Intervention: lapatinib ditosylate; laboratory biomarker analysis
Intervention description: Given PO; Correlative studies
Intervention MeSH terms: Lapatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 57.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well lapatinib works in treating patients with locally
      advanced or metastatic biliary tract or liver cancer that cannot be removed by surgery.
      Lapatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically or cytologically confirmed, surgically unresectable
             biliary cancer (gallbladder, ampullary, intra or extrahepatic bile duct) OR patients
             must have surgically unresectable HCC and who are not candidates for percutaneous
             ethanol injection or radio frequency ablation (RFA); patients must have histological
             or cytological confirmation of HCC

          -  Patients must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded) as >=
             20 mm with conventional techniques or as >= 10 mm with spiral CT scan; if a patient
             has undergone TACE, ethanol or RFA ablation then new lesions need to be present in the
             liver, if there are no other sites of disease

          -  Patients may have received prior therapy as follows:

               -  No more than one prior chemotherapy regimen for metastatic or recurrent disease
                  will be allowed; prior chemotherapy for earlier stage disease (neoadjuvant,
                  adjuvant, or concurrent with radiation therapy) will be allowed in addition to
                  prior chemotherapy for recurrent metastatic disease; TACE is considered one
                  regimen; at least 3 weeks must have elapsed since prior therapy, and toxicities
                  of therapy should have resolved to =< Grade 1

               -  Patients may have received prior radiation therapy; three weeks must have elapsed
                  since the completion of prior radiation therapy and patients must have recovered
                  from all toxicities; measurable disease must either be outside the previous
                  radiation field, or progressing within a radiated field, or a new lesion must be
                  present

               -  There must be no plans for the patient to receive concurrent hormonal, biologic,
                  or radiation therapy to measurable lesions

               -  Patients who have had prior treatment with EGFR targeting therapies are
                  ineligible

               -  Patients may not be receiving any other investigational agents or receiving
                  concurrent anticancer therapy

          -  Life expectancy of greater than 12 weeks

          -  ECOG performance status less than or equal to 2 (Karnofsky >= 60%)

          -  Patients who have scores that fall into Childs B or C groups are excluded

          -  Patients must have organ and marrow function as defined below:

          -  Leukocytes >= 3000/mcL

          -  Absolute neutrophil count >= 1,500/mcL

          -  Platelets >= 75,000/mcL

          -  Total bilirubin < 2 mg/dl

          -  AST(SGOT)/ALT(SGPT) =< 5.0 X upper limit of institutional normal (ULN)

          -  PT prolongation < 4 secs above ULN (unless taking warfarin)

          -  Creatinine =< ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with
             creatinine levels above institutional normal

          -  Cardiac ejection fraction above the lower limit of normal as measured by
             echocardiogram or MUGA scan; note that baseline and on- treatment scans should be
             performed using the same modality and preferably at the same institution

          -  Adherence to the requirements for concomitant medications classified as CYP3A4
             inducers or inhibitors

          -  HIV-positive patients receiving combination anti-retroviral therapy are excluded from
             the study because of possible pharmacokinetic interactions with GW572016; appropriate
             studies will be undertaken in patients receiving combination anti-retroviral therapy
             when indicated

          -  Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided
             there is appropriate close INR monitoring is in place; if medically appropriate and
             treatment available, the investigator may also consider switching these patients to
             low molecular weight (LMW) heparin, where an interaction with GW572016 is not expected

          -  The effects of GW572016 on the developing human fetus at the recommended therapeutic
             dose are unknown; for this reason, women of child-bearing potential and men must agree
             to use adequate contraception (hormonal or barrier method of birth control or
             abstinence) prior to study entry and for the duration of study participation; should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she should inform her treating physician immediately

          -  Pregnant women are excluded from this study because GW572016 is member of the
             4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or
             abortifacient effects; because there is an unknown but potential risk for adverse
             events in nursing infants secondary to treatment of the mother with GW572016,
             breastfeeding should be discontinued if the mother is treated with GW572016

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Able to swallow and retain oral medication

          -  Patients with known brain metastases (Scans are not necessary to exclude brain
             metastasis) should be 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

          -  Patients with 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, will be excluded

          -  Patients with GI tract disease resulting in an inability to take oral medication,
             malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
             affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative
             colitis) are also ineligible

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to GW572016 (i.e inhibitors of EGF and HER2- /neu) will render patients
             ineligible