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Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

Primary Purpose

Adult Primary Hepatocellular Carcinoma, Advanced Adult Primary Liver Cancer, Localized Unresectable Adult Primary Liver Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
lapatinib ditosylate
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST
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.

Secondary Outcome Measures

Progression-free Survival
Toxicity Profile Assessed Using NCI CTCAE Version 3.0
Percentage of patients with Adverse events accordng to NCI CTCAE version 3.0
Median Overall Survival
Overall Survival
Target-EGFR/EGFR-P Protein Expression
EGFR (exons 18-21)
Expression Profile and Mutations of Genes Critical for EGFR and ERBB2 Signaling Pathways

Full Information

First Posted
April 5, 2005
Last Updated
April 8, 2015
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00107536
Brief Title
Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer
Official Title
A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
October 2005 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
26 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
lapatinib ditosylate
Other Intervention Name(s)
GSK572016, GW-572016, GW2016, Lapatinib, Tykerb
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST
Description
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.
Time Frame
Up to 3 years
Secondary Outcome Measure Information:
Title
Progression-free Survival
Time Frame
up to 6 months
Title
Toxicity Profile Assessed Using NCI CTCAE Version 3.0
Description
Percentage of patients with Adverse events accordng to NCI CTCAE version 3.0
Time Frame
Up to 3 years
Title
Median Overall Survival
Time Frame
Up to 3 years
Title
Overall Survival
Time Frame
up to 12.6 months
Title
Target-EGFR/EGFR-P Protein Expression
Description
EGFR (exons 18-21)
Time Frame
Up to 3 years
Title
Expression Profile and Mutations of Genes Critical for EGFR and ERBB2 Signaling Pathways
Time Frame
Up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tanios Bekaii-Saab
Organizational Affiliation
Ohio State University Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22433475
Citation
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.
Results Reference
background
PubMed Identifier
19737952
Citation
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.
Results Reference
result

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Lapatinib Ditosylate in Treating Patients With Unresectable Liver or Biliary Tract Cancer

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