A Study of Tarceva (Erlotinib) in Sequential Combination With Gemcitabine as First Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer

A Randomized, Open-label Study of the Effect of First Line Treatment With Tarceva in Sequential Combination With Gemcitabine, Compared to Gemcitabine Monotherapy, on Progression-free Survival in Elderly or ECOG PS of 2 Patients With Advanced Non-small Cell Lung Cancer.

This 2 arm study will compare the efficacy and safety of sequential treatment with Tarceva and gemcitabine, and of gemcitabine monotherapy, as first line treatment of elderly patients, or patients with ECOG performance status of 2, with advanced non-small cell lung cancer.Patients will be randomized to receive either sequential gemcitabine 1250mg/m2/day on days 1 and 8 + Tarceva 150mg po on days 15-28 of each 4 week cycle, or gemcitabine monotherapy 1000mg/m2/day on days 1, 8 and 15 of each 4 week cycle. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Study Overview

• Status: Terminated
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: erlotinib [Tarceva]; Drug: gemcitabine; Drug: gemcitabine

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Port Macquarie, New South Wales, Australia, 2444
    • Randwick, New South Wales, Australia, 2031
    • Sydney, New South Wales, Australia, 2139
    • Sydney, New South Wales, Australia, 2747
    • Tweed Heads, New South Wales, Australia, NSW 2485
    • Wollongong, New South Wales, Australia, 2500
  • Queensland
    • Brisbane, Queensland, Australia, 4029
    • Greenslopes, Queensland, Australia, 4120
    • Woolloongabba, Queensland, Australia, 4102
  • South Australia
    • Richmond, South Australia, Australia, 3121
    • Terrace Gardens, South Australia, Australia, 5065
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
  • Victoria
    • Bendigo, Victoria, Australia, 3550
    • Heidelberg, Victoria, Australia, 3084
    • Melbourne, Victoria, Australia, 3002
    • Wodonga, Victoria, Australia, 3690
  • Western Australia
    • Fremantle, Western Australia, Australia, 6160

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult patients, >=70 years of age or with ECOG PS of 2;
• advanced (stage IIIB or IV)non-small cell lung cancer;
• no prior systemic chemotherapy for advanced NSCLC or prior treatment with HER-axis targeted drugs.

Exclusion Criteria:

• active brain metastasis or spinal cord suppression;
• unstable systemic disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: erlotinib [Tarceva]; 150mg po on days 15-28 of each 4 week cycle; Drug: gemcitabine; 1250mg/m2/day on days 1 and 8 of each 4 week cycle; Drug: gemcitabine; 1000mg/m2/day on days 1, 8 and 15 of each 4 week cycle
Active Comparator: 2	Drug: gemcitabine; 1250mg/m2/day on days 1 and 8 of each 4 week cycle; Drug: gemcitabine; 1000mg/m2/day on days 1, 8 and 15 of each 4 week cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Disease Progression or Death	Progression-free survival (PFS) was defined as the time from randomization to the date of first documentation of progressive disease (PD), according to Response Evaluation Criteria in Solid Tumors (RECIST) version (V) 1.0, or date of death from any cause. PD was defined for target lesions (TLs) as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded since the start of treatment, and for non-target lesions (NTLs) as unequivocal progression of NTLs. Participants without documented PD were censored at the date of last tumor assessment, the last date recorded in the drug log, or the last date of follow-up the participant was known to be progression free, whichever was last. Participants without a post-Baseline (BL) tumor assessment who were known to be alive were censored at the date of randomization.	BL, Day 22 of Cycles 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (12 months after randomization of the last participant).
PFS	The median time, in weeks, between randomization and PFS event. Participants without documented PD were censored at the date of last tumor assessment, the last date recorded in the drug log, or the last date of follow-up the participant was known to be progression free, whichever was last. Participants without a post-BL tumor assessment who were known to be alive were censored at the date of randomization. PFS was estimated by using Kaplan-Meier methodology.	BL, Day 22 of Cycles 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (up to 2 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Confirmed Complete Response (CR) or Partial Response (PR) According to RECIST V 1.0	As per RECIST V 1.0: for TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the SLD of TLs taking as reference the BL SLD. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. The 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper Method.	BL, Day 22 of Cycle 2, 4, and 6 (28-day cycles), every 2 months thereafter until disease progression, participant withdrawal, or study termination (12 months after randomization of the last participant).
Percentage of Participants With Non-Progression at Weeks 8 and 16	Non-progression was defined as CR, PR, or stable disease according to RECIST V 1.0: for TLs, CR was defined as the disappearance of all TLs, PR was defined as at least a 30% decrease in the SLD of TLs taking as reference the BL SLD, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD recorded since the start of treatment. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels, and SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above the normal limits. The 95% CI for one-sample binomial was determined using the Pearson-Clopper method.	Weeks 8 and 16
Percentage of Participants Who Died		BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.
Overall Survival (OS)	OS was defined as the median time, in weeks, between randomization and death due to any cause. Participants without documented death were censored at the last date recorded in the drug log, or the last date of follow-up the participant was known to be alive, whichever was last. Participants without a post-BL assessment who were known to be alive were censored at the date of randomization. OS was estimated using Kaplan-Meier methodology.	BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.
Duration of Response	Duration of response was defined as the time between the first documentation of CR or PR (whichever status was recorded first as assessed by the RECIST V 1.0) until the date of documented disease progression or death. Participants with no documented disease progression or death after confirmed CR or PR were censored at the date of the last tumor assessment or last date of follow-up when the participant was known to be progression free, whichever was last.	BL, Days 1, 8, and 15 of Cycles 1-6 (28-day cycles), every 28 days thereafter until death, participant withdrawal, or study termination up to 2 years.

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 6, 2009
• First Submitted That Met QC Criteria: July 15, 2009
• First Posted (Estimate): July 16, 2009

Study Record Updates

• Last Update Posted (Estimate): April 2, 2015
• Last Update Submitted That Met QC Criteria: April 1, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protein Kinase Inhibitors; Gemcitabine; Erlotinib Hydrochloride
• Other Study ID Numbers: ML22429