a two-stage phase 1 dose escalation pharmacokinetic study of tarceva in patients with stage iiib/iv non-small cell lung cancer who continue to smoke after failure of one or two prior chemotherapy regimens

Conditions: NSCLC

Summary: this is a multicenter, open-label, randomized phase 1 study of escalating doses of tarceva in patients with advanced nsclc who currently smoke. part i will establish the maximum tolerated dose (mtd) of tarceva in current smokers. in part ii, patients will be randomized 1:1 to two treatment groups: arm a (tarceva mtd established in part i) and arm b (150 mg tarceva daily). patients in both arms will be treated for two weeks and then have pharmacokinetic samples collected on day 14. part ii is open as of nov-2006.


Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed diagnosis of stage iiib/iv nsclc; * must have received 1 or 2 prior chemotherapy regimens for advanced nsclc and now have progressive disease; * must have recovered from any treatment-related toxicities prior to registration, except for alopecia, grade 1 fatigue, or grade 1 neurotoxicity; * a current cigarette smoker (minimum of 10 cigarettes per day for \>= 1 year and have a positive test for cotinine) despite advice and support to quit; * age \>= 18 years; * ecog ps 0-1 and predicted life expectancy \>= 12 weeks; * previous surgery is permitted provided that wound healing has occurred prior to registration; * adequate hematopoietic, hepatic and renal function defined as follows: anc \>= 1.5 x 10\^9/l, platelets \>= 100 x 10\^9/l, bilirubin \<= 1.5 x uln, alt \<= 2.5 x uln (or 5 x uln in case of liver metastases), creatinine \<= 1.5 x uln; * no prior treatment with tarceva or gefitinib (or other drug with significant activity against egfr (eg, cetuximab and/or zd6474)); * patients with reproductive potential must practice effective contraceptive measures throughout the study. women of child-bearing potential must provide a negative pregnancy test within 14 days prior to registration; * accessible for repeat dosing and follow-up. exclusion criteria: * any concurrent anticancer cytostatic or cytotoxic chemotherapy; * concomitant cyp3a4 or cyp1a2 inducers/inhibitors (or during 14 days prior to study) with the exception of tobacco; * other active malignancies, unless disease-free and without cancer-specific therapy for at least the last 5 years. basal or squamous cell skin cancers are not excluded; * significant history of cardiac disease unless the disease is well-controlled; * active or uncontrolled infections or serious illnesses or medical conditions that could interfere with the patient's ongoing participation in the study; * history of any psychiatric condition that might impair the patient's ability to understand or comply with the requirements; of the study or to provide informed consent. * gastrointestinal abnormalities, including inability to take oral medication, requirement for iv alimentation, active peptic ulcer or prior surgical procedures affecting absorption; * clinically significant ophthalmologic abnormalities; * pregnant or breast-feeding females. males or females not practicing effective birth control; * symptomatic brain metastases which are not stable, require steroids, or that have required radiation within the last 28 days; * history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drug;

Keywords: lung cancer erlotinib nsclc smokers