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

NCT ID: NCT00356889

Last Updated: 2014-05-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-31
• Study Completion Date: 2010-06-30

Brief Summary

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.

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

erlotinib hydrochloride

Intervention Type: DRUG

Given orally, 150 mg, once daily.

bevacizumab

Intervention Type: BIOLOGICAL

Given IV, 5mg/kg on days 1 and 15 every cycle

Interventions

erlotinib hydrochloride

Given orally, 150 mg, once daily.

Intervention Type: DRUG

bevacizumab

Given IV, 5mg/kg on days 1 and 15 every cycle

Intervention Type: BIOLOGICAL

Other Intervention Names

CP-358,774; erlotinib; OSI-774; anti-VEGF humanized monoclonal antibody; anti-VEGF monoclonal antibody; Avastin; rhuMAb VEGF

Eligibility Criteria

Inclusion 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Schelman

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

MC044G

Identifier Type: -

Identifier Source: secondary_id

CDR0000484566

Identifier Type: REGISTRY

Identifier Source: secondary_id

N01CM17104

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00115

Identifier Type: -

Identifier Source: org_study_id

NCT01646957

Identifier Type: -

Identifier Source: nct_alias

NCT01664416

Identifier Type: -

Identifier Source: nct_alias