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

NSCLC Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00294736
• Other study ID #: OSI-774-107
• Secondary ID: 2005-003883-46
• Status: Completed
• Phase: Phase 1
• First received: February 17, 2006
• Last updated: August 6, 2012
• Start date: November 2005
• Est. completion date: September 2007

Study information

• Verified date: August 2012
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 57
• Est. completion date: September 2007
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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;

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Drug:
• Tarceva
Dose Escalation: 150-350+ mg/day

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	University of Edinburgh,Division of Oncology,	Edinburgh	Scotland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Sir Bobby Robson Cancer Trials Research Centre	Newcastle upon Tyne
United Kingdom	Department of Oncology	Sheffield
United Kingdom	Royal Marsden Hospital	Sutton
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
OSI Pharmaceuticals

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To establish the MTD of Tarceva in currently smoking patients with stage IIIB/IV NSCLC.		2 years	No
Secondary	To evaluate the survival of currently smoking patients with stage IIIB/IV NSCLC when given Tarceva at the MTD and 150 mg.		2 years	Yes