Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer
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; Carcinoma, Hepatocellular; Liver Neoplasms; Gallbladder Neoplasms; Bile Duct Neoplasms; Cholangiocarcinoma; Recurrence
Intervention: lapatinib ditosylate; laboratory biomarker analysis
Intervention description: 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: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. This phase II trial is studying how well lapatinib ditosylate works
      in treating patients with unresectable liver or biliary tract cancer
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of 1 of the following:

               -  Hepatocellular carcinoma (hepatoma)

                    -  Child-Pugh classification score ≤ 7

               -  Biliary tract carcinoma

          -  Surgically unresectable disease

          -  Measurable disease

               -  At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
                  OR ≥ 10 mm by spiral CT scan

          -  Fresh tissue or paraffin embedded tissue from tumor blocks available

          -  No ampulla of Vater tumors

          -  No known brain metastases

          -  Performance status - ECOG 0-1

          -  Performance status - Karnofsky 60-100%

          -  More than 12 weeks

          -  Absolute neutrophil count ≥ 1,500/mm^3

          -  Platelet count ≥ 75,000/mm^3

          -  Bilirubin ≤ 2 times upper limit of normal (ULN)

          -  AST and ALT ≤ 3 times ULN

          -  Albumin ≥ 2.5 mg/dL

          -  INR ≤ 1.5 (for patients not receiving an anticoagulant)

          -  Live metastases or stable chronic liver disease allowed

          -  No current active hepatic or biliary disease except for Gilbert's syndrome or
             asymptomatic gallstone

          -  Creatinine ≤ 2 mg/dL

          -  Ejection fraction normal by echocardiogram or MUGA

          -  No unstable angina pectoris

          -  No cardiac arrhythmia

          -  Able to swallow and retain oral medication

          -  No gastrointestinal (GI) tract disease resulting in an inability to take oral
             medication

          -  No malabsorption syndrome

          -  No requirement for IV alimentation

          -  No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception

          -  No significant traumatic injury within the past 3 weeks

          -  No active or ongoing infection

          -  No history of allergic reaction attributed to compounds of similar chemical or
             biological composition to lapatinib

          -  No psychiatric illness or social situation that would preclude study compliance

          -  No other uncontrolled illness

          -  No other malignancy within the past 3 years except adequately treated basal cell or
             squamous cell skin cancer or carcinoma in situ of the cervix

          -  More than 4 weeks since prior biologic therapy

          -  More than 4 weeks since prior immunotherapy

          -  See Radiotherapy

          -  More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

          -  No prior cumulative doxorubicin dose > 450 mg/m^2

          -  At least 14 days since prior and no concurrent glucocorticoids (e.g., dexamethasone or
             equivalent [dose > 1.5 mg/day])

          -  More than 4 weeks since prior radiotherapy

          -  More than 12 weeks since prior radiotherapy with or without a fluoropyrimidine as a
             radiosensitizer (for patients with biliary carcinoma only)

          -  No prior surgical procedure affecting absorption

          -  More than 3 weeks since prior major surgery

          -  Recovered from all prior therapy

          -  No more than 1 prior systemic anticancer therapy, including chemoembolization

          -  No prior epidermal growth factor receptor-targeting therapy

          -  More than 6 weeks since prior cryotherapy, radiofrequency ablation, ethanol injection,
             transarterial chemoembolization, or photodynamic therapy AND meets both of the
             following criteria:

               -  Indicator lesion is outside the area of prior treatment OR there is clear
                  evidence of disease progression associated with the sole indicator lesion

               -  Edges of indicator lesion are clearly distinct by CT scan

          -  At least 7 days since prior and no concurrent H2 inhibitors or proton pump inhibitors

               -  Concurrent antacids allowed provided they are administered > 1 hour before and >
                  1 hour after study drug administration

          -  At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the
             following:

               -  Clarithromycin

               -  Erythromycin

               -  Troleandomycin

               -  Delaviridine

               -  Ritonavir

               -  Indinavir

               -  Saquinavir

               -  Nelfinavir

               -  Amprenavir

               -  Lopinavir

               -  Itraconazole

               -  Ketoconazole

               -  Voriconazole

               -  Fluconazole (doses ≤ 150 mg/day are allowed)

               -  Nefazodone

               -  Fluvoxamine

               -  Verapamil

               -  Diltiazem

               -  Cimetidine

               -  Aprepitant

               -  Grapefruit and grapefruit juice

               -  Bitter orange

          -  At least 6 months since prior and no concurrent amiodarone

          -  At least 14 days since prior and no concurrent CYP3A4 inducers, including any of the
             following:

               -  Phenytoin

               -  Carbamazepine

               -  Phenobarbital

               -  Oxcarbazepine

               -  Efavirenz

               -  Nevirapine

               -  Rifampin

               -  Rifabutin

               -  Rifapentine

               -  Roxithromycin

               -  Telithromycin

               -  Hypericum perforatum (St. John's wort)

               -  Modafinil

          -  No concurrent combination antiretroviral therapy for HIV-positive patients

          -  No other concurrent investigational agents

          -  No other concurrent anticancer therapy

          -  Concurrent oral anticoagulants (e.g., coumadin or warfarin) allowed provided there is
             increased vigilance in monitoring INR