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Adult Primary Hepatocellular CarcinomaPhase 2NCT00107536

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

A Phase 2 study testing lapatinib ditosylate and laboratory biomarker analysis in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
lapatinib ditosylate and laboratory biomarker analysis
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
Oct 2005to May 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically confirmed diagnosis of 1 of the following:
  • Hepatocellular carcinoma (hepatoma)
  • Child-Pugh classification score ≤ 7
  • Biliary tract carcinoma
  • Surgically unresectable disease
  • Measurable disease
Show all 99Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

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

    Columbus, Ohio, 43210

Other trials in United States

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

  1. 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.

Being tested
lapatinib ditosylate, laboratory biomarker analysis
Medical subject headings
Carcinoma, Hepatocellular, Bile Duct Neoplasms, Gallbladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • lapatinib ditosylateDrug

    Also called GSK572016, GW-572016, GW2016, Lapatinib

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00107536
Study groupRoleWhat they receive
Arm IExperimentalPatients receive oral lapatinib ditosylate once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: lapatinib ditosylate; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 3 years

Secondary outcomes (6)

  1. Progression-free Survival

    Measured: up to 6 months

  2. Toxicity Profile Assessed Using NCI CTCAE Version 3.0

    Percentage of patients with Adverse events accordng to NCI CTCAE version 3.0

    Measured: Up to 3 years

  3. Median Overall Survival

    Measured: Up to 3 years

  4. Overall Survival

    Measured: up to 12.6 months

  5. Target-EGFR/EGFR-P Protein Expression

    EGFR (exons 18-21)

    Measured: Up to 3 years

  6. Expression Profile and Mutations of Genes Critical for EGFR and ERBB2 Signaling Pathways

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Apr 2005 (estimated)
  2. Study startOct 2005
  3. Primary completionMay 2009
  4. Study completionMay 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00107536
Sponsor's protocol ID
NCI-2012-01464
Other IDs
OSU 0447, N01CM62207, N01CM62201, CDR0000420830
Status last verified
Mar 2015
First submitted
5 Apr 2005
Last updated
29 Apr 2015

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.

    PubMed 22433475

  • 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.

    PubMed 19737952

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing lapatinib ditosylate and laboratory biomarker analysis in people with Adult Primary Hepatocellular Carcinoma and Advanced Adult Primary Liver Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 99 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Apr 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Patients Demonstrating Objective Response (PR+CR) as Defined by RECIST (time frame: Up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00107536, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2015.

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