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

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

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.

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.

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