Triapine as First-Line or Second-Line Therapy in Treating Patients With Locally Advanced or Metastatic Cancer of the Pancreas

Study Overview
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Brief Summary
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This phase II trial is studying how well triapine works as first-line or second-line therapy in treating patients with locally advanced or metastatic adenocarcinoma (cancer) of the pancreas. Drugs used in chemotherapy, such as triapine, work in different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the 3- and 6-month survival rate of patients with locally advanced or metastatic adenocarcinoma of the pancreas treated with 3-AP (Triapine^®) as first- or second-line therapy. SECONDARY OBJECTIVES: I. Determine the toxicity and tolerability of this drug in these patients. II. Determine the time to treatment failure in patients treated with this drug. III. Determine overall survival and disease progression in patients treated with this drug. IV. Determine tumor response in patients treated with this drug. V. Determine laboratory studies that will increase our understanding of Triapine and its effects on cellular processes. OUTLINE: This is a multicenter study. Patients are stratified according to prior chemotherapy (yes vs no). Patients receive triapene IV over 2 hours on days 1-4 and 15-18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 3-6 months for 3 years.

Official Title
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A Phase II Study Of Triapine For Advanced Adenocarcinoma Of The Pancreas

Conditions
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Acinar Cell Adenocarcinoma of the Pancreas, Duct Cell Adenocarcinoma of the Pancreas, Recurrent Pancreatic Cancer, Stage III Pancreatic Cancer, Stage IV Pancreatic Cancer

Intervention / Treatment
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* Drug: triapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the pancreas Unresectable disease Locally advanced or metastatic disease At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan Measurable lesions outside prior radiotherapy field OR measurable lesions actively growing in the site of prior radiotherapy No prior chemotherapy OR previously treated with 1, and only 1, gemcitabine-containing regimen for metastatic, unresectable, or locally advanced pancreatic cancer Adjuvant therapy not considered prior chemotherapy if all treatment was completed > 6 months before tumor recurrence No known brain metastases Performance status - ECOG 0-2 At least 6 weeks Absolute neutrophil count >= 1,500/mm^3 Platelet count >= 75,000/mm^3 AST =< 3 times upper limit of normal (ULN) Bilirubin =< 1.5 times ULN Creatinine =< 1.5 times ULN Creatinine clearance > 60 mL/min No uncontrolled congestive heart failure No unstable angina pectoris No cardiac arrhythmia No pulmonary disease requiring oxygen Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No glucose-6-phosphate dehydrogenase (G6PD) deficiency (for patients of African, Asian, or Mediterranean origin or ancestry) No active or ongoing infection No hypersensitivity or severe allergic reaction to 3-AP (Triapine®) or related compounds No concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No other concurrent antineoplastic therapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational therapy for the malignancy

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: Treatment (triapene)<br>Patients receive triapene IV over 2 hours on days 1-4 and 15-18. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: triapine<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival in patients receiving triapine as first-line therapy | The point estimate of the success rates will be calculated as the number of successes divided by the number of evaluable patients, with confidence intervals calculated by the method of Duffy and Santner. | 6 months | 
| Survival in patients receiving triapine as second-line therapy | The point estimate of the success rates will be calculated as the number of successes divided by the number of evaluable patients, with confidence intervals calculated by the method of Duffy and Santner. | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events assessed using CTCAE version 3.0 |  | Up to 3 years | 
| Time to treatment failure |  | Time from the date of randomization to the date at which the patient is removed from treatment due to progression, toxicity, or refusal, assessed up to 3 years | 
| Overall survival |  | Up to 3 years | 
| Time to disease progression | The distribution of time to progression will be estimated using the method of Kaplan-Meier. | Time from registration to documentation of disease progression, assessed up to 3 years | 
| Confirmed tumor response, defined to be a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart |  | 6 months (first 6 courses of treatment) |