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

Study Overview
=================
Brief 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.

Official Title
-----------------
A Two-Stage Phase 1 Dose Escalation Pharmacokinetic Study of Tarceva® (Erlotinib) 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

Intervention / Treatment
-----------------
* Drug: Tarceva


Participation Criteria
=================
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;

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Arm A (Tarceva MTD established in Part I) | Drug: Tarceva<br>* Dose Escalation: 150-350+ mg/day<br>|
| Experimental: Arm B<br>Arm B (150 mg Tarceva daily). | Drug: Tarceva<br>* Dose Escalation: 150-350+ mg/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the MTD of Tarceva in currently smoking patients with stage IIIB/IV NSCLC. |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the survival of currently smoking patients with stage IIIB/IV NSCLC when given Tarceva at the MTD and 150 mg. |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
lung cancer, erlotinib, NSCLC, smokers