- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00107536
Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer
A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas
Study Overview
Status
Conditions
- 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
- Adult Primary Hepatocellular Carcinoma
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Ohio
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Columbus, Ohio, United States, 43210
- Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I
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.
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Correlative studies
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST
Time Frame: Up to 3 years
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PR (Partial Response) definded as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
CR (Complete Response) is defined as the disappearance of all target lesions.
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Up to 3 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival
Time Frame: up to 6 months
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up to 6 months
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Toxicity Profile Assessed Using NCI CTCAE Version 3.0
Time Frame: Up to 3 years
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Percentage of patients with Adverse events accordng to NCI CTCAE version 3.0
|
Up to 3 years
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Median Overall Survival
Time Frame: Up to 3 years
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Up to 3 years
|
|
Overall Survival
Time Frame: up to 12.6 months
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up to 12.6 months
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Target-EGFR/EGFR-P Protein Expression
Time Frame: Up to 3 years
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EGFR (exons 18-21)
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Up to 3 years
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Expression Profile and Mutations of Genes Critical for EGFR and ERBB2 Signaling Pathways
Time Frame: Up to 3 years
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Up to 3 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tanios Bekaii-Saab, Ohio State University Comprehensive Cancer Center
Publications and helpful links
General Publications
- Peck J, Wei L, Zalupski M, O'Neil B, Villalona Calero M, Bekaii-Saab T. HER2/neu may not be an interesting target in biliary cancers: results of an early phase II study with lapatinib. Oncology. 2012;82(3):175-9. doi: 10.1159/000336488. Epub 2012 Mar 15.
- Bekaii-Saab T, Markowitz J, Prescott N, Sadee W, Heerema N, Wei L, Dai Z, Papp A, Campbell A, Culler K, Balint C, O'Neil B, Lee RM, Zalupski M, Dancey J, Chen H, Grever M, Eng C, Villalona-Calero M. A multi-institutional phase II study of the efficacy and tolerability of lapatinib in patients with advanced hepatocellular carcinomas. Clin Cancer Res. 2009 Sep 15;15(18):5895-901. doi: 10.1158/1078-0432.CCR-09-0465. Epub 2009 Sep 8.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Digestive System Neoplasms
- Liver Diseases
- Gallbladder Diseases
- Biliary Tract Diseases
- Bile Duct Diseases
- Biliary Tract Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Recurrence
- Cholangiocarcinoma
- Liver Neoplasms
- Gallbladder Neoplasms
- Bile Duct Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Lapatinib
Other Study ID Numbers
- NCI-2012-01464
- N01CM62201 (U.S. NIH Grant/Contract)
- N01CM62207 (U.S. NIH Grant/Contract)
- OSU 0447
- CDR0000420830 (Registry Identifier: PDQ (Physician Data Query))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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