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A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas

Phase 2
18 Years
Not Enrolling
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

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Trial Information

A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas


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.


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.

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

- No malabsorption syndrome

- No requirement for IV alimentation

- No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative

- 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

- 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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Proportion of patients demonstrating objective response (PR+CR) as defined by RECIST

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Tanios Bekaii-Saab

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

October 2005

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Liver Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Biliary Tract Neoplasms
  • Carcinoma, Hepatocellular



Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240