Gold Sodium Thiomalate in Treating Patients With Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Gold sodium thiomalate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I trial is studying the side effects and best dose of gold sodium thiomalate in treating patients with advanced non-small cell lung cancer.

Detailed Description
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OBJECTIVES: To determine the maximum tolerated dose of gold sodium thiomalate in patients with advanced non-small cell lung cancer. To describe the toxicities associated with this treatment. To describe any preliminary evidence of biologic activity. To further assess the correlation between PKCι expression and the antitumor effects of gold sodium thiomalate. To study the association of clinical (toxicity and/or tumor response or activity) with pharmacokinetic/pharmacodynamic parameters. To describe anti-proliferative activity of gold sodium thiomalate through 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging. OUTLINE: This is a dose-escalation study of gold sodium thiomalate. Patients receive gold sodium thiomalate intramuscularly on days 1, 8, 15 and 22. Treatment repeats every 4 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive gold sodium thiomalate once every 4 weeks until a total cumulative dose of 1 gram is delivered. Blood samples are collected at baseline and prior to therapy in weeks 3, 5, 7, 9, and 11. Samples are analyzed by mass spectometry for pharmacokinetics. Paraffin-embedded tumor tissue samples are analyzed for PKC_l expression and antitumor activity. Antiproliferative effects of gold sodium thiomalate are analyzed by 3-deoxy-3-[^18F]-fluorothymidine positron emission tomography imaging.

Official Title
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A Phase I Dose Escalation Study of the PKC Inhibitor, Aurothiomalate (ATM) in Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: gold sodium thiomalate
* Genetic: gene expression analysis
* Other: fluorine F 18 fluorothymidine
* Other: mass spectrometry
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed advanced non-small cell lung cancer No known standard therapy for disease that is potentially curative or definitely capable of extending life expectancy No symptomatic or worsening CNS metastases despite optimal therapy PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 weeks ANC ≥ 1,500/µL Platelet count ≥ 100,000/µL Total bilirubin ≤ 2 times upper limit of normal (ULN) AST ≤ 3 times ULN (5 times ULN if liver involvement) Creatinine ≤ 1.2 times ULN Hemoglobin ≥ 9.0 g/dL Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be willing to provide blood and tissue samples No uncontrolled infection No New York Heart Association class III or IV heart disease No known allergy to gold sodium thiomalate PRIOR CONCURRENT THERAPY: Recovered from acute, reversible effects of prior chemotherapy regardless of interval since last treatment No prior chemotherapy within the past 3 weeks No prior mitomycin C or nitrosoureas within the past 6 weeks No prior immunotherapy within the past 3 weeks No prior biologic therapy within the past 3 weeks No prior radiotherapy within the past 3 weeks No prior radiotherapy to > 25% of bone marrow No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (i.e., utilized for a non-FDA-approved indication and in the context of a research investigation) No concurrent prophylactic colony stimulating factors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gold sodium thiomalate|nan|
|Genetic: gene expression analysis|nan|
|Other: fluorine F 18 fluorothymidine|nan|
|Other: mass spectrometry|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  |  | 
| Toxicity |  |  | 
| Biologic activity |  |  | 
| Correlate PKCl expression with antitumor effects of gold sodium thiomalate |  |  | 
| Correlate toxicity and/or tumor response or activity with pharmacokinetic and pharmacodynamic parameters |  |  | 
| Anti-proliferative activity of gold sodium thiomalate by PET scan |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, recurrent non-small cell lung cancer