3-AP in Treating Patients With Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This phase I trial is studying the side effects and best dose of 3-AP in treating patients with advanced or metastatic solid tumors. 3-AP may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description
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OBJECTIVES: I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors. II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients. III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess tumoral expression of genes involved in response and resistance to 3-AP. V. Observe and record any tumor response in these patients. OUTLINE: This is a multicenter, dose-escalation study. Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples for pharmacokinetic analysis are collected periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP during course 1. After completion of study treatment, patients are followed periodically.

Official Title
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A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: triapine
* Other: pharmacological study
* Procedure: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Criteria: Must be able to swallow Histologically confirmed solid tumor Advanced or metastatic disease Measurable or evaluable disease No known active CNS metastases ECOG performance status 0-1 Life expectancy > 3 months Progressive disease during >= 1 prior standard therapy OR disease unlikely to respond to any currently available therapies Patients with previously treated CNS metastases who have no evidence of new CNS metastases AND are stable for >= 2 months are eligible Platelet count >= 100,000/mm^3 Hemoglobin >= 10 g/dL (transfusions allowed) Absolute neutrophil count >= 1,500/mm^3 ALT and AST =< 2.5 times upper limit of normal (ULN) Alkaline phosphatase =< 2.5 times ULN Creatinine =< 1.5 mg/dL OR creatinine clearance >= 50 mL/min Bilirubin normal PT/PTT =< 1.5 times ULN FEV1 >= 1.2 L Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception 2 weeks prior to and during study treatment No mental deficits and/or psychiatric history that may preclude study treatment No active heart disease, including any of the following: myocardial infarction within the past 3 months, symptomatic coronary artery disease or heart block, uncontrolled congestive heart failure No moderate to severe compromise of pulmonary function No active infection No other life-threatening illness No active coagulation disorder other than occult blood No known positivity for glucose-6-phosphate dehydrogenase (G6PD) deficiency Recovered from prior treatment Prior gemcitabine allowed More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) More than 3 weeks since prior radiotherapy or any other treatment for this cancer No prior 3-AP No concurrent radiotherapy No other concurrent investigational agent

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: Arm I<br>Patients will receive a 2-hour infusion of 3-AP once in week 1. Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks. Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown. | Drug: triapine<br>* Given IV and orally<br>* Other names: OCX-191;Other: pharmacological study<br>* correlative study<br>* Other names: pharmacological studies;Procedure: laboratory biomarker analysis<br>* Correlative study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0 |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum pharmacokinetics of oral triapine | Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate. The relationship of the AUC to the dose will be assessed by least-square regression analysis. | Baseline, day 4, and day 8 |