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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00107536
First received: April 5, 2005
Last updated: January 7, 2013
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
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
Drug: lapatinib ditosylate
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Efficacy and Tolerability of GW572016 in Patients With Advanced Hepatocellular and Biliary Carcinomas

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Proportion of patients demonstrating objective response (PR+CR) as defined by RECIST [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Toxicity profile assessed using NCI CTCAE version 3.0 [ Time Frame: Up to 3 years ] [ Designated as safety issue: Yes ]
  • Median overall survival [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Target-EGFR/EGFR-P protein expression [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Expression profile and mutations of genes critical for EGFR and ERBB2 signaling pathways [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Enrollment: 70
Study Start Date: October 2005
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: lapatinib ditosylate
Other Names:
  • GSK572016
  • GW-572016
  • GW2016
  • Lapatinib
  • Tykerb
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00107536

Locations
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Tanios Bekaii-Saab Ohio State University Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00107536     History of Changes
Other Study ID Numbers: NCI-2012-01464, OSU 0447, N01CM62207, N01CM62201, CDR0000420830
Study First Received: April 5, 2005
Last Updated: January 7, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Bile Duct Neoplasms
Carcinoma
Carcinoma, Hepatocellular
Gallbladder Neoplasms
Liver Neoplasms
Adenocarcinoma
Bile Duct Diseases
Biliary Tract Diseases
Biliary Tract Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Gallbladder Diseases
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Lapatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014