A Phase II Trial of Triapine (NSC #663249) in Combination With Gemcitabine as Second Line Treatment of Non-Small Cell Lung Cancer

Inclusion Criteria:

Patients must have histologically confirmed non-small cell lung cancer (NSCLC); cytology alone is not acceptable
Patients must have progressive or recurrent NSCLC, and must have failed one and only one prior cytotoxic chemotherapy regimen for advanced disease; patients must not have received prior gemcitabine chemotherapy
Patients must have measurable disease, as defined by RECIST, within 4 weeks prior to registration
Patients must have an ECOG performance status of 0 or 1
Bilirubin < 1.5 x upper limit of normal
AST (SGOT) < 3 x upper limit of normal
Serum creatinine =< 1.5 mg/dL, or calculated creatinine clearance >= 60 mL/min
Absolute granulocyte count >= 1500/mm3 and WBC >= 3000/mm^3
Hemoglobin >= 9 g/L
Platelet count >= 100,000/mm^3
Patients must have completed any radiation therapy >= 3 weeks prior to registration
Patients must have completed prior cytotoxic chemotherapy >= 3 weeks prior to registration and have recovered from adverse effects from the chemotherapy to =< Grade 1, or baseline
Patients with brain metastases which have been treated are eligible if the patient is > 3 weeks post completion of treatment for their brain metastases, and patient is neurologically stable; patients with previous brain metastases who have not yet received therapy specifically intended for their brain metastases are not eligible to enroll in this protocol
Life expectancy greater than 3 months
Pregnant women are excluded from this study because Triapine® is a heterocyclic carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Triapine®, breastfeeding should be discontinued if the mother is treated with Triapine®; women must not be pregnant or breastfeeding due to the absence of information regarding the use of these agents in these populations; a negative serum pregnancy test is required within 14 days of study entry; the effects of Triapine® on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because heterocyclic carboxaldehyde thiosemicarbazones as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination antiretroviral therapy are excluded from the study because of possible pharmacokinetic interactions with Triapine®
Patients must not have an active second malignancy
Patients must not have, at the time of registration, uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements; furthermore, since hypoxemia may cause serious adverse events in persons with serious cardiac and/or pulmonary disease, patients at the time of registration with a history of myocardial infarction within the prior 6 months, or with symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring medical intervention (with the exception of chronic, stable, asymptomatic atrial fibrillation), or pulmonary disease requiring oxygen are excluded
Patients must not have dementia or active psychosis
Patients must not have used any investigational agent in the month before study enrollment
Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to Triapine® or other agents used in this study
Patients must not have a clinical history of G6PD (glucose-6-phosphate dehydrogenase) deficiency; persons at high risk for this condition (patients of African, Asian, or Mediterranean origin/ancestry) must undergo specific clinical testing at protocol entry for this condition; patients testing positive for G6PD deficiency are excluded from protocol entry