Bevacizumab and Erlotinib Hydrochloride in Treating Patients With Metastatic or Unresectable Biliary Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00356889
First received: July 26, 2006
Last updated: May 12, 2014
Last verified: April 2013
  Purpose

This phase II trial is studying how well giving bevacizumab together with erlotinib hydrochloride works in treating patients with metastatic or unresectable biliary tumors. 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 hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab and erlotinib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving bevacizumab together with erlotinib hydrochloride may kill more tumor cells.


Condition Intervention Phase
Cholangiocarcinoma of the Extrahepatic Bile Duct
Cholangiocarcinoma of the Gallbladder
Gastrointestinal Cancer
Recurrent Extrahepatic Bile Duct Cancer
Recurrent Gallbladder Cancer
Unresectable Extrahepatic Bile Duct Cancer
Unresectable Gallbladder Cancer
Drug: erlotinib hydrochloride
Biological: bevacizumab
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 Trial of Bevacizumab and Erlotinib in Patients With Advanced Biliary Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number of Confirmed Tumor Responses. [ Time Frame: After 6 courses of treatment. Each course lasts 28 days. ] [ Designated as safety issue: No ]

    Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the target lesions.

    A confirmed tumor response is defined to be either a Complete Response or a Partial Response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. Confirmed tumor responses will be evaluated using the first 6 cycles of treatment. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment and had one post-baseline disease assessment will be evaluable for response. Forty-nine of the 53 eligible patients had at least one post-baseline disease assessment and were evaluable for this endpoint.



Secondary Outcome Measures:
  • Survival Time [ Time Frame: From registration to death due to any cause, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier (1958).

  • Time to Disease Progression [ Time Frame: From registration to documentation of disease progression, assessed up to 3 years ] [ Designated as safety issue: No ]
    Estimated using the method of Kaplan-Meier (1958).

  • Duration of Response [ Time Frame: From the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented, assessed up to 3 years ] [ Designated as safety issue: No ]
    Point estimates and 95% confidence intervals were calculated using the method of Duffy and Santner (1987).


Enrollment: 56
Study Start Date: May 2006
Study Completion Date: June 2010
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab and Erlotinib Hydrochloride

Patients receive 5 mg/kg bevacizumab IV over 30-90 minutes on days 1 and 15 and 150 mg 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.

Drug: erlotinib hydrochloride
Given orally, 150 mg, once daily.
Other Names:
  • CP-358,774
  • erlotinib
  • OSI-774
Biological: bevacizumab
Given IV, 5mg/kg on days 1 and 15 every cycle
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

I. Evaluate time to progression in these patients.

II. Evaluate overall and progression-free survival of these patients.

III. Evaluate the adverse events associated with this regimen. OUTLINE: This is an open-label, multicenter study.

Patients receive bevacizumab intravenously (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.

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

  Eligibility

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

Criteria:

  • Absolute neutrophil count >= 1,500/mm3
  • 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

    • 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
  • Life expectancy >= 3 months
  • ECOG performance status 0-2
  • Platelet count >= 75,000/mm3
  • Total bilirubin =< 2 times 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
    • Requirement for IV alimentation
  • No concurrent illness or medical condition, including any of the following:

    • Active peptic ulcer disease;
    • Serious or nonhealing wound, ulcer, or bone fracture;
    • GI bleed that required procedural intervention within the past 3 months
  • No concurrent illness or medical condition, including any of the following:

    • 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
  • No abnormalities of the cornea
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No clinically significant cardiovascular disease
  • More than 4 weeks since prior chemotherapy or radiotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
  • No significant traumatic injury within the past 28 days
  • No prior systemic anticancer therapy for metastatic gallbladder or bile duct cancer
  • More than 28 days since prior major surgery [Note: Insertion of a vascular access device is not considered major/minor surgery]
  • More than 2 weeks since prior minor surgery [Note: Insertion of a vascular access device is not considered major/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 or any other CYP3A4 inducer, such as rifampin or Hypericum perforatum
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational agents or other concurrent anticancer therapies
  • No concurrent prophylactic hematopoietic colony-stimulating factors
  • Concurrent full-dose anticoagulants 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
  • AND (continued from above) No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels, gastrointestinal ulcerations, or known varices)
  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: NCT00356889

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: William Schelman Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00356889     History of Changes
Obsolete Identifiers: NCT01646957, NCT01664416
Other Study ID Numbers: NCI-2009-00115, MC044G, CDR0000484566, N01CM17104
Study First Received: July 26, 2006
Results First Received: February 22, 2013
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Cholangiocarcinoma
Bile Duct Neoplasms
Gastrointestinal Neoplasms
Gallbladder Neoplasms
Biliary Tract Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Gastrointestinal Diseases
Gallbladder Diseases
Bevacizumab
Antibodies
Antibodies, Monoclonal
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors

ClinicalTrials.gov processed this record on September 18, 2014