Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Lapatinib in Treating Patients With Unresectable Liver or Biliary Tract Cancer

Basic Trial Information

Special Category: NCI Web site featured trial

Objectives

Primary

1. Determine the objective response rate (complete response and partial response) in patients with unresectable hepatocellular carcinoma or biliary tract carcinoma treated with lapatinib.

Secondary

1. Determine 6-month disease-free survival in patients treated with this drug.
2. Determine the toxicity profile of this drug in these patients.
3. Determine median overall survival and 6- and 12-month survival rates in patients treated with this drug.
4. Correlate target epidermal growth factor receptor gene and protein expression and the genes that regulate cell cycle and apoptosis with clinical outcome in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• 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

Prior/Concurrent Therapy:

Biologic therapy

• More than 4 weeks since prior biologic therapy
• More than 4 weeks since prior immunotherapy

Chemotherapy

• See Radiotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No prior cumulative doxorubicin dose > 450 mg/m²

Endocrine therapy

• At least 14 days since prior and no concurrent glucocorticoids (e.g., dexamethasone or equivalent [dose > 1.5 mg/day])

Radiotherapy

• 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)

Surgery

• No prior surgical procedure affecting absorption
• More than 3 weeks since prior major surgery

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

  OR

• Karnofsky 60-100%

Life expectancy

• More than 12 weeks

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 75,000/mm³

Hepatic

• 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

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• Ejection fraction normal by echocardiogram or MUGA
• No unstable angina pectoris
• No cardiac arrhythmia

Gastrointestinal

• 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)

Other

• 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

Expected Enrollment

A total of 70 patients will be accrued for this study within 1 year.

Outcomes

Response rate every 2 months after completion of study treatment

Progression-free survival after completion of study treatment
Median overall survival after complection of study treatment
Survival at 6 and 12 months after completion of study treatment
Toxicity every month

Outline

This is a multicenter study.

Patients receive oral lapatinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Bekaii-Saab T, Markowitz J, Prescott N, et al.: A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas. Clin Cancer Res 15 (18): 5895-901, 2009.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Tanios Bekaii-Saab, MD, Protocol chair		Ph: 614-293-9863

Related Information

Featured trial article

Registry Information
Official Title		A Phase II Study of Efficacy and Tolerability of GW572016 in Patients with Advanced Hepatocellular and Biliary Carcinomas
Trial Start Date		2005-10-18
Trial Completion Date		2008-12-23
Registered in ClinicalTrials.gov		NCT00107536
Date Submitted to PDQ		2005-02-09
Information Last Verified		2009-06-15
NCI Grant/Contract Number		CA16058, CA76576

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