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Bevacizumab and Erlotinib in Treating Patients With Metastatic or Unresectable Biliary Tumors
This study has been suspended.
Sponsors and Collaborators: Mayo Clinic
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00356889
  Purpose

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and erlotinib may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with erlotinib may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with erlotinib works in treating patients with metastatic or unresectable biliary tumors.


Condition Intervention Phase
Extrahepatic Bile Duct Cancer
Gallbladder Cancer
Drug: bevacizumab
Drug: erlotinib hydrochloride
Procedure: immunohistochemistry staining method
Procedure: laboratory biomarker analysis
Procedure: molecular diagnostic method
Procedure: mutation analysis
Procedure: protein expression analysis
Phase II

MedlinePlus related topics: Cancer Gallbladder Cancer
Drug Information available for: Erlotinib Erlotinib hydrochloride Bevacizumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Trial of Bevacizumab and Erlotinib in Patients With Advanced Biliary Tumors

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

Primary Outcome Measures:
  • Proportion of confirmed tumor responses [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: May 2006
Estimated Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Evaluate the objective response rate in patients with metastatic or unresectable cholangiocarcinoma treated with bevacizumab and erlotinib hydrochloride.

Secondary

  • Evaluate time to progression in these patients.
  • Evaluate overall and progression-free survival of these patients.
  • Evaluate the adverse events associated with this regimen.

Tertiary

  • Determine the presence of epidermal growth factor receptor (EGFR) mutations in tumor tissue and correlate this with outcome.
  • Evaluate expression of molecules involved in EGFR signal transduction, including EGFR, P-EGFR, AKT, P-AKT, mitogen-activated protein kinase (MAPK), P-MAPK, and HER2-neu by immunohistochemistry and correlate these with patient outcome measures.
  • Determine the levels of vascular endothelial growth factor (VEGF) and VEGF receptors in tumor tissue and plasma and correlate these with patient outcome measures.

OUTLINE: This an open-label, multicenter study.

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Tumor tissue and blood specimens are collected periodically for correlative studies. Specimens are examined by immunohistochemistry for epidermal growth factor receptor (EGFR) and P-EGFR protein levels; AKT p-AKT, mitogen-activated protein kinase (MAPK) and P-MAPK protein levels; and vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 protein levels. EGFR mutations are detected by laser capture microdissection. Enzyme-linked immunosorbent assay is used to measure total and free serum VEGF levels.

After completion of study therapy, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed cholangiocarcinoma or gallbladder carcinoma

    • Metastatic or surgically unresectable disease
  • Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured as ≥ 2.0 cm with conventional techniques or as > 1.0 cm with spiral CT scan

    • Spiral CT scan imaging must be used for pre- and post-treatment tumor measurements of lesions measuring ≥ 1.0 cm to < 2.0 cm
    • Clinical lesions will only be considered measurable when they are superficial (e.g., skin nodules, palpable lymph nodes)
    • Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung.
  • No ampulla of Vater tumors
  • No evidence of CNS disease, including primary brain tumor or brain metastasis

PATIENT CHARACTERISTICS:

  • Life expectancy ≥ 3 months
  • ECOG performance status 0-2
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 75,000/mm³
  • Total bilirubin ≤ 2 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN
  • Creatinine ≤ 2 mg/dL
  • Albumin ≥ 2.5 g/dL
  • Alkaline phosphatase ≤ 5 times ULN
  • Urine protein:creatinine ratio < 1.0 OR 24-hour urine protein < 1000 mg
  • No concurrent illness or medical condition, including any of the following:

    • Impairment of gastrointestinal (GI) function or disease that may significantly alter the absorption of erlotinib hydrochloride (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
    • Requirement for IV alimentation
    • Active peptic ulcer disease
    • Serious or nonhealing wound, ulcer, or bone fracture
    • GI bleed that required procedural intervention (e.g., variceal banding, surgical shunt, transvenous intrahepatic porto-systemic shunt) within the past 3 months
    • Abdominal fistula, GI perforation, or intra-abdominal abscess within the past 28 days
    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Psychiatric illness or social situation that would limit study compliance
  • No other malignancy within the past 3 years except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer, or stage I or II cancer currently in complete remission
  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No abnormalities of the cornea based on any of the following:

    • History (e.g., dry eye syndrome, Sjögren's syndrome)
    • Congenital abnormality (e.g., Fuch's dystrophy)
    • Abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose),
    • Abnormal corneal sensitivity test (Schirmer test or similar tear production test)
  • Not pregnant
  • Negative pregnancy test
  • No nursing during and for at least 6 months after completion of study treatment
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
  • No clinically significant cardiovascular disease, including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Uncontrolled hypertension
    • Myocardial infarction or unstable angina within the past 6 months
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Unstable angina pectoris
    • Peripheral vascular disease
  • No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

  • No prior systemic anticancer therapy for metastatic gallbladder or bile duct cancer
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • More than 28 days since prior major surgery*
  • More than 2 weeks since prior minor surgery*
  • More than 7 days since prior core biopsy
  • No concurrent major surgery
  • No other concurrent chemotherapy, immunotherapy, radiotherapy, or any other therapy or supportive care considered investigational
  • No concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, phenobarbital) or any other CYP3A4 inducer, such as rifampin or Hypericum perforatum (St. John's wort)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents
  • No other concurrent anticancer therapies
  • No concurrent prophylactic hematopoietic colony-stimulating factors
  • Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided PT/INR is > 1.5 and both of the following criteria are met:

    • In-range INR on a stable dose of oral anticoagulant OR on a stable dose of low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal ulcerations, or known varices) NOTE: *Insertion of a vascular access device is not considered major/minor surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00356889

Locations
United States, District of Columbia
Howard University Cancer Center
Washington, District of Columbia, United States, 20060
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Wisconsin
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164
Sponsors and Collaborators
Mayo Clinic
Investigators
Study Chair: Kyle D. Holen, MD University of Wisconsin, Madison
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000484566, MAYO-MC044G, NCI-7024
Study First Received: July 26, 2006
Last Updated: January 14, 2009
ClinicalTrials.gov Identifier: NCT00356889  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
cholangiocarcinoma of the extrahepatic bile duct
cholangiocarcinoma of the gallbladder
recurrent gallbladder cancer
unresectable gallbladder cancer
recurrent extrahepatic bile duct cancer
unresectable extrahepatic bile duct cancer

Study placed in the following topic categories:
Erlotinib
Gallbladder Diseases
Bile duct cancer, extrahepatic
Cholangiocarcinoma
Biliary Tract Neoplasms
Digestive System Neoplasms
Bevacizumab
Recurrence
Gall bladder cancer
Digestive System Diseases
Bile Duct Diseases
Biliary Tract Diseases
Gastrointestinal Neoplasms
Gallbladder Neoplasms
Bile Duct Neoplasms

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Enzyme Inhibitors
Angiogenesis Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions
Neoplasms
Neoplasms by Site
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009