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

NCT00356889 | Completed Phase 2 Results DMC

• 4 other identifiers: NCI-2009-00115MC044GCDR0000484566N01CM17104
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Confirmed Tumor Responses.

  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.

  After 6 courses of treatment. Each course lasts 28 days.

Secondary Outcomes (3)

• Survival Time

  From registration to death due to any cause, assessed up to 3 years

• Time to Disease Progression

  From registration to documentation of disease progression, assessed up to 3 years

• Duration of Response

  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

Study Arms (1)

Bevacizumab and Erlotinib Hydrochloride

EXPERIMENTAL

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; Biological: bevacizumab

Interventions

erlotinib hydrochloride DRUG

Given orally, 150 mg, once daily.

Also known as: CP-358,774, erlotinib, OSI-774

Bevacizumab and Erlotinib Hydrochloride

bevacizumab BIOLOGICAL

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

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Bevacizumab and Erlotinib Hydrochloride

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Gastrointestinal Neoplasms; Bile Duct Neoplasms; Gallbladder Neoplasms

Interventions

Erlotinib Hydrochloride; Bevacizumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Gallbladder Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: William Schelman, M.D.
• Organization: University of Wisconsin Cancer Center

wrs@medicine.wisc.edu

Study Officials

• William Schelman

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2006
• First Posted: July 27, 2006
• Study Start: May 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: June 1, 2010
• Last Updated: May 28, 2014
• Results First Posted: May 20, 2013

Record last verified: 2013-04

Locations

US (1)