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About
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
Full description
PRIMARY OBJECTIVES:
I. To evaluate the objective response rate (complete response [CR] + partial response [PR]) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria in each group of patients.
SECONDARY OBJECTIVES:
I. To evaluate the progression free survival at 6 months. II. To evaluate the toxicity profile of this treatment in each group of patients.
III. To evaluate median overall survival, 6 and 12 months survival rates. IV. To assess target-epidermal growth factor receptor (EGFR)/EGFR-P protein expression and the genes that regulate the cell cycle and apoptosis, which are either downstream of or cross-talk with the EGFR signaling pathway, to explore their association with clinical outcome.
V. To measure expression profile and mutations of genes critical for EGFR and (v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (ERBB2 signaling pathways with particular relevance to GW572016, and to explore new gene-drug relationships as relating to hepatocellular and biliary carcinomas.
OUTLINE: This is a multicenter study.
Patients receive oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 1 year.
Enrollment
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Inclusion and exclusion criteria
Inclusion Criteria:
Histologically confirmed diagnosis of 1 of the following:
Hepatocellular carcinoma (hepatoma)
Biliary tract carcinoma
Surgically unresectable disease
Measurable disease
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:
At least 7 days since prior and no concurrent H2 inhibitors or proton pump inhibitors
At least 7 days since prior and no concurrent CYP3A4 inhibitors, including any of the following:
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:
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
Primary purpose
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Interventional model
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26 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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