Stage II Gallbladder Cancer, Stage IIIA Gallbladder Cancer, Stage IIIB Gallbladder Cancer, Stage IVA Gallbladder Cancer, Stage IVB Gallbladder Cancer
Conditions
Brief summary
This phase II trial is studying how well giving 3-AP together with gemcitabine works in treating patients with unresectable or metastatic bile duct or gallbladder cancer. Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may help gemcitabine kill more cancer cells by making them more sensitive to the drug.
Detailed description
OBJECTIVES: I. To determine the objective response rates for the combination of triapine and gemcitabine in patients with primary tumors of the biliary ducts and gall bladder. II. To assess the toxicities and recovery from toxicities for patients with biliary duct and gall bladder tumors treated with the combination of triapine and gemcitabine. III. To determine the survival and progression free survival of patients with biliary and gall bladder tumors treated with the combination of triapine and gemcitabine. OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to bilirubin levels (normal vs abnormal). Patients receive 3-AP (Triapine) IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 1 additional course beyond CR. Patients are followed every 3 months for up to 2 years.
Interventions
DRUGtriapine
Given IV
DRUGgemcitabine
Given IV
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
Yes
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the biliary ducts that is unresectable and/or metastatic; this can include unresectable or metastatic carcinomas of the Ampulla of Vater. In addition, unresectable or metastatic gall bladder carcinoma will be allowed * Measurable disease * No prior chemotherapy * Life expectancy of greater than 3 months * ECOG performance status =\< 2 (Karnofsky \>= 60%) * Leukocytes \>= 3,000/uL * Absolute neutrophil count \>= 1,500/uL * Platelets \>= 100,000/uL * Creatinine within normal institutional limits * Patients may have mildly abnormal liver function defined as a total bilirubin \> ULN and =\< 3x the institutional upper limits of normal (includes CTCAE v.3 grades 1-2 hyperbilirubinemia) * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Patients may not be receiving any other investigational agents * Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events * History of allergic reactions attributed to compounds of similar chemical or biologic composition to Triapine or gemcitabine * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia * Uncontrolled pulmonary disease including asthma, chronic bronchitis and COPD or with requirements for chronic oxygen use * Pregnant or lactating women * HIV infection * Patients with G6PD deficiency will be excluded in view of the potential for methemoglobinemia * Psychiatric illness/social situations that would limit compliance with study requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate According to RECIST Criteria | Up to 2 years | Tumor response was assessed every eight weeks by CT scan using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disapperance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall response (OR) = CR+PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival | Up to 2 years | PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression. |
| Overall Survival | Up to 2 years | — |
Countries
United States
Participant flow
Recruitment details
A total of 35 patients were enrolled from 7 institutions between December 2003 and August 2007
Pre-assignment details
A total of 2 patients did not receive treatment
Participants by arm
| Arm | Count |
|---|---|
| Stratum A Normal Liver Triapine, Gemcitabine Triapine IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15, repeat every 28 days
triapine: Given IV
gemcitabine: Given IV | 23 |
| Stratum B Abnormal Liver Triapine, Gemcitabine Triapine IV over 4 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15, repeat every 28 days
triapine: Given IV
gemcitabine: Given IV | 10 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 9 | 7 |
Baseline characteristics
| Characteristic | Stratum A Normal Liver Triapine, Gemcitabine | Stratum B Abnormal Liver Triapine, Gemcitabine | Total |
|---|---|---|---|
| Age, Continuous | 57 years | 67.5 years | 62.3 years |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 20 participants | 10 participants | 30 participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 17 Participants |
| Sex: Female, Male Male | 12 Participants | 4 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 22 / 23 | 10 / 10 |
| serious Total, serious adverse events | 21 / 23 | 10 / 10 |
Outcome results
Primary
Response Rate According to RECIST Criteria
Tumor response was assessed every eight weeks by CT scan using RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions: Complete Response (CR), Disapperance of all target lesions; Partial Response (PR), \>= 30% decrease in the sum of the longest diameter of target lesions; Overall response (OR) = CR+PR.
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Stratum A Normal Liver Function Triapine, Gemcitabine | Response Rate According to RECIST Criteria | 3 participants |
| Stratum B Abnormal Liver Function Triapine, Gemcitabine | Response Rate According to RECIST Criteria | 0 participants |
Secondary
Overall Survival
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum A Normal Liver Function Triapine, Gemcitabine | Overall Survival | 10.3 months |
| Stratum B Abnormal Liver Function Triapine, Gemcitabine | Overall Survival | 3.6 months |
Secondary
Progression Free Survival
PFS will be measured from the time of the patient's initial best response (PR or CR) until documented progression.
Time frame: Up to 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Stratum A Normal Liver Function Triapine, Gemcitabine | Progression Free Survival | 3.7 months |
| Stratum B Abnormal Liver Function Triapine, Gemcitabine | Progression Free Survival | 3.6 months |