3-AP and Gemcitabine as Second-Line Therapy in Treating Patients With Stage III or Stage IV Recurrent Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: 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. Giving more than one drug may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving 3-AP together with gemcitabine as second-line therapy works in treating patients with recurrent stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the objective response rate in patients with stage III or IV recurrent non-small cell lung cancer treated with 3-AP (Triapine®) and gemcitabine as second-line therapy. Secondary Determine the response duration, median time to progression, and overall survival of patients treated with this regimen. Determine the toxicity of this regimen in these patients. Determine the effect of 3-AP (Triapine®) on gemcitabine pharmacokinetics and cellular uptake into peripheral mononuclear cells in patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients are stratified according to participating center. Patients receive 3-AP (Triapine®) IV over 4 hours and gemcitabine IV over 30 minutes on days 1, 8, and 15*. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. NOTE: *For course 1 only, gemcitabine is administered alone on day 1 and in combination with 3-AP (Triapine®) on days 8 and 15. Patients are followed every 3 months for up to 2 years. PROJECTED ACCRUAL: A total of 15-31 patients will be accrued for this study within 7.5-21 months.

Official Title
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A Randomized Phase II Study Of Triapine® Alone Versus Triapine and Gemcitabine As Second-Line Treatment Of Advanced Non-Small-Cell-Lung Cancer In Patients Who Had Prior Gemcitabine With Evaluation Of The Effect Of Triapine® On Gemcitabine Pharmacokinetics and Cellular Uptake In Peripheral Mononuclear Cells

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: triapine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed* non-small cell lung cancer (NSCLC) Stage III or IV disease One of the following cellular types: Adenocarcinoma Non-diffuse bronchoalveolar cell carcinoma Large cell carcinoma Squamous cell carcinoma NOTE: *A repeat biopsy of any accessible tumor site is required if > 5 years have elapsed since the initial diagnosis Progressive disease after 1 prior gemcitabine-containing chemotherapy regimen for stage III or IV NSCLC and must have achieved, at least once, a partial response, complete response, or stable disease during therapy Not a primary non-responder and experienced only progressive disease during gemcitabine-containing chemotherapy Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No known brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 No glucose-6-phosphate dehydrogenase (G6PD) deficiency Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) ALT ≤ 2.5 times ULN (5 times ULN if liver metastases are present) Renal Creatinine ≤ 1.5 times ULN OR Creatinine clearance ≥ 50 mL/min Cardiovascular No prior uncontrolled cardiac disease No myocardial infarction within the past 12 months No symptomatic congestive heart failure No coronary artery disease No cardiac arrhythmia Pulmonary No uncontrolled symptomatic pulmonary disease No pulmonary disease that requires oxygen therapy Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except completely treated carcinoma in situ of the cervix or nonmelanoma skin cancer No prior allergic reaction attributed to compounds of similar chemical or biological composition to study agents No other concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy See Disease Characteristics More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered Endocrine therapy Not specified Radiotherapy More than 4 weeks since prior radiotherapy and recovered Surgery Not specified Other No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer agents or therapies

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: gemcitabine hydrochloride|nan|
|Drug: triapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective tumor response as assessed by RECIST criteria |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity as assessed by NCI CTCAE v3.0 |  |  | 
| Overall survival |  |  | 
| Median time to progression |  |  | 
| Duration of overall response |  |  | 
| Pharmacokinetics |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer, squamous cell lung cancer