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A Phase II Study of GW572016 (Lapatanib) in Locally Advanced or Metastatic Hepato-Biliary Cancers

Phase 2
18 Years
Not Enrolling
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

Thank you

Trial Information

A Phase II Study of GW572016 (Lapatanib) in Locally Advanced or Metastatic Hepato-Biliary Cancers


I. The goal of this study is to determine the objective response rate of GW572016 in
patients with biliary cancer and hepatocellular cancer (HCC).


I. Determine the overall survival of patients entered onto study. II. Quantitative and
qualitative toxicities of the patient population treated with GW572016.

III. Determine the progression free survival of patients. IV. To perform molecular and
pharmacogenomic correlative studies that will identify specific patient subsets that benefit
from GW572016 therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to tumor site
(biliary tree cancer [includes ampullary, bile duct, and gall bladder cancer] vs
hepatocellular cancer).

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

Patients are followed for survival.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed, surgically unresectable
biliary cancer (gallbladder, ampullary, intra or extrahepatic bile duct) OR patients
must have surgically unresectable HCC and who are not candidates for percutaneous
ethanol injection or radio frequency ablation (RFA); patients must have histological
or cytological confirmation of HCC

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan; if a patient
has undergone TACE, ethanol or RFA ablation then new lesions need to be present in
the liver, if there are no other sites of disease

- Patients may have received prior therapy as follows:

- No more than one prior chemotherapy regimen for metastatic or recurrent disease
will be allowed; prior chemotherapy for earlier stage disease (neoadjuvant,
adjuvant, or concurrent with radiation therapy) will be allowed in addition to
prior chemotherapy for recurrent metastatic disease; TACE is considered one
regimen; at least 3 weeks must have elapsed since prior therapy, and toxicities
of therapy should have resolved to =< Grade 1

- Patients may have received prior radiation therapy; three weeks must have
elapsed since the completion of prior radiation therapy and patients must have
recovered from all toxicities; measurable disease must either be outside the
previous radiation field, or progressing within a radiated field, or a new
lesion must be present

- There must be no plans for the patient to receive concurrent hormonal, biologic,
or radiation therapy to measurable lesions

- Patients who have had prior treatment with EGFR targeting therapies are

- Patients may not be receiving any other investigational agents or receiving
concurrent anticancer therapy

- Life expectancy of greater than 12 weeks

- ECOG performance status less than or equal to 2 (Karnofsky >= 60%)

- Patients who have scores that fall into Childs B or C groups are excluded

- Patients must have organ and marrow function as defined below:

- Leukocytes >= 3000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 75,000/mcL

- Total bilirubin < 2 mg/dl

- AST(SGOT)/ALT(SGPT) =< 5.0 X upper limit of institutional normal (ULN)

- PT prolongation < 4 secs above ULN (unless taking warfarin)

- Creatinine =< ULN OR creatinine clearance >= 50 mL/min/1.73 m^2 for patients with
creatinine levels above institutional normal

- Cardiac ejection fraction above the lower limit of normal as measured by
echocardiogram or MUGA scan; note that baseline and on- treatment scans should be
performed using the same modality and preferably at the same institution

- Adherence to the requirements for concomitant medications classified as CYP3A4
inducers or inhibitors

- HIV-positive patients receiving combination anti-retroviral therapy are excluded from
the study because of possible pharmacokinetic interactions with GW572016; appropriate
studies will be undertaken in patients receiving combination anti-retroviral therapy
when indicated

- Patients requiring oral anticoagulants (coumadin, warfarin) are eligible provided
there is appropriate close INR monitoring is in place; if medically appropriate and
treatment available, the investigator may also consider switching these patients to
low molecular weight (LMW) heparin, where an interaction with GW572016 is not

- The effects of GW572016 on the developing human fetus at the recommended therapeutic
dose are unknown; for this reason, women of child-bearing potential and men must
agree to use adequate contraception (hormonal or barrier method of birth control or
abstinence) prior to study entry and for the duration of study participation; should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating physician immediately

- Pregnant women are excluded from this study because GW572016 is member of the
4-anilinoquinazoline class of kinase inhibitors with the potential for teratogenic or
abortifacient effects; because there is an unknown but potential risk for adverse
events in nursing infants secondary to treatment of the mother with GW572016,
breastfeeding should be discontinued if the mother is treated with GW572016

- Ability to understand and the willingness to sign a written informed consent document

- Able to swallow and retain oral medication

- Patients with known brain metastases (Scans are not necessary to exclude brain
metastasis) should be excluded from this clinical trial because of their poor
prognosis and because they often develop progressive neurologic dysfunction that
would confound the evaluation of neurologic and other adverse events

- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements, will be excluded

- Patients with GI tract disease resulting in an inability to take oral medication,
malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative
colitis) are also ineligible

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GW572016 (i.e inhibitors of EGF and HER2- /neu) will render patients

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Time Frame:

Up to 5 years

Safety Issue:


Principal Investigator

Ramesh Ramanathan

Investigator Role:

Principal Investigator

Investigator Affiliation:

UC Davis Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2004

Completion Date:

Related Keywords:

  • 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
  • Carcinoma
  • Liver Neoplasms
  • Gallbladder Neoplasms
  • Bile Duct Neoplasms
  • Carcinoma, Hepatocellular



UC Davis Comprehensive Cancer Center Sacramento, California  95817