Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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This phase II trial is studying how well trastuzumab works in treating patients with locally advanced or metastatic gallbladder cancer or bile duct cancer that cannot be removed by surgery. Monoclonal antibodies, such as trastuzumab, 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

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the objective response rate and duration of objective response in patients with HER2/neu-positive advanced gallbladder or biliary tract cancer treated with trastuzumab (Herceptin). SECONDARY OBJECTIVES: I. Assess the safety and tolerability of this drug in these patients. II. Assess the progression-free survival and overall survival of patients treated with this drug. OUTLINE: Patients receive trastuzumab intravenously over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months.

Official Title
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A Phase II Study Trastuzumab (NSC 688097) in Her2/Neu Positive Cancer of the Gallbladder or Biliary Tract (NCI 7756)

Conditions
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Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Malignant Neoplasm, Recurrent Extrahepatic Bile Duct Cancer, Recurrent Gallbladder Cancer, Unresectable Extrahepatic Bile Duct Cancer, Unresectable Gallbladder Cancer

Intervention / Treatment
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* Biological: trastuzumab
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Criteria: Adenocarcinoma of the gallbladder Recurrent extrahepatic bile duct cancer Recurrent gallbladder cancer Unresectable extrahepatic bile duct cancer Adenocarcinoma of the extrahepatic bile duct Unresectable gallbladder cancer Prior surgery and radiotherapy allowed At least 28 days since prior chemotherapy (6 weeks for nitrosoureas and mitomycin C) and recovered No other concurrent investigational agents, chemotherapy, radiotherapy, or hormonal therapy Concurrent hormones administered for nondisease-related conditions (e.g., insulin for diabetes) allowed No concurrent corticosteroids or anticonvulsants Concurrent steroids administered for antiemesis, adrenal failure, or septic shock allowed No concurrent combination antiretroviral therapy for HIV-positive patients Histologically or cytologically confirmed adenocarcinoma of the gallbladder or bile duct, meeting all of the following criteria: locally advanced or metastatic disease that is unresectable Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral computed tomography (CT) scan Tumor that recurs within a previously irradiated field is considered measurable disease if recurrence is documented and measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria Tumor must be Her2/neu positive by Fluorescence in situ hybridization (FISH)testing No symptomatic brain metastases The Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100% Absolute neutrophil count (ANC) >= 1,500/mm^3 Fertile patients must use effective contraception prior to, during, and for >= 3 months after completion of study treatment Creatinine =< 2 times upper limits of normal (ULN) OR creatinine clearance >= 60 mL/min No other active malignancy Left Ventricular Ejection Fraction (LVEF) >= 50% No concurrent uncontrolled illness No ongoing or active infection requiring systemic IV antibiotics on day 1 of treatment No symptomatic New York Heart Association class III-IV congestive heart failure No unstable angina pectoris No unstable cardiac arrhythmia requiring medication No more than 1 prior systemic chemotherapy regimen White Blood Count (WBC) >= 3,000/mm^3 Platelet count >= 40,000/mm^3 Bilirubin =< 4 mg/dL Aspartate aminotransferase and alanine aminotransferase (AST and ALT) =< 5 times upper limit of normal (ULN) Not pregnant or nursing Negative pregnancy test

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trastuzumab<br>Participants receive trastuzumab loading dose 8 mg/kg intravenous (IV) over 30-90 minutes on day 1 and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Biological: trastuzumab<br>* For HER-2/neu positive biopsies, trastuzumab was administered intravenously, once every 3 weeks, at a loading first dose at 8 mg/kg over 90 minutes, and subsequent maintenance doses of 6 mg/kg over 90 minutes then every 30 minutes starting at the third dose.<br>* Other names: MOAB HER2;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (Complete and Partial Response) | Response assessed using imaging-based evaluation at baseline then following single agent trastuzumab administered over 21 day cycle, re-staging done following 2 cycles. Response Evaluation Criteria in Solid Tumors defined as Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Baseline to 63 days or until disease progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Percentage of participants who have achieved complete response, partial response and stable disease | Up to 3.5 years | 
| Number of Participant With Toxicity Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Participant toxicity for study as assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 reported in Results Adverse Event Reporting of record. | Up to 3 years | 
| Overall Survival | Length of time from date of starting treatment that participants are still alive | Up to 3.5 years |