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
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALtrastuzumab
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.
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response (Complete and Partial Response) | Baseline to 63 days or until disease progression | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | Up to 3.5 years | Percentage of participants who have achieved complete response, partial response and stable disease |
| Number of Participant With Toxicity Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | Up to 3 years | 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. |
| Overall Survival | Up to 3.5 years | Length of time from date of starting treatment that participants are still alive |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: May 30, 2007 to June 15, 2009. All recruitment done in medical clinics.
Pre-assignment details
Of the 53 participants pre-screened only four participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab 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. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Clinical Disease Progression | 1 |
Baseline characteristics
| Characteristic | Trastuzumab |
|---|---|
| Age, Continuous | 52 years |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 0 / 4 |
Outcome results
Primary
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.
Time frame: Baseline to 63 days or until disease progression
Population: Only those participants who had measurable disease present at baseline, received at least one cycle of therapy, and had disease re-evaluated considered evaluable for response; therefore one participant was inevaluable.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab | Objective Response (Complete and Partial Response) | Complete Response | 1 participants |
| Trastuzumab | Objective Response (Complete and Partial Response) | Partial Response | 0 participants |
| Trastuzumab | Objective Response (Complete and Partial Response) | Progressive Disease | 1 participants |
| Trastuzumab | Objective Response (Complete and Partial Response) | Stable Disease | 1 participants |
Secondary
Disease Control Rate
Percentage of participants who have achieved complete response, partial response and stable disease
Time frame: Up to 3.5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Disease Control Rate | 67 percentage of participants |
Secondary
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.
Time frame: Up to 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab | Number of Participant With Toxicity Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | 3 participants |
Secondary
Overall Survival
Length of time from date of starting treatment that participants are still alive
Time frame: Up to 3.5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab | Overall Survival | 65 weeks |