Erlotinib in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer (TOPICAL)

A Randomised, Placebo-Controlled Trial of Erlotinib in Patients With Advanced NSCLC Unsuitable for Chemotherapy

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether erlotinib is more effective than a placebo in treating non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying erlotinib to see how well it works compared to a placebo in treating patients with stage III or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: erlotinib hydrochloride; Drug: Matched placebo

Detailed Description

OBJECTIVES:

Primary

• Compare survival of patients with stage IIIB or IV non-small cell lung cancer that is not suitable for first-line chemotherapy treated with erlotinib vs placebo.

Secondary

• Compare progression-free survival and response rate.
• Compare toxicity.
• Compare the quality of life.
• Compare cost-effectiveness.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral erlotinib once daily for up to 24 months.
• Arm II: Patients receive oral placebo once daily for up to 24 months. Quality of life is assessed periodically.

After completion of study treatment, patients are followed periodically for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A total of 664 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 670
• Phase: Phase 3

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, NW1 2ND
      • London Lung Cancer Group

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer

  • Advanced disease (stage IIIB or IV)
  • Diagnosis within 62 days prior to randomization

• Not suitable for first-line chemotherapy, as defined by the following criteria*:

  • ECOG performance status 2-3
  • ECOG performance status 0-1 AND creatinine clearance < 60 mL/min
• NOTE: *These criteria do not imply that all such patients are unsuitable for chemotherapy; patients are considered unsuitable on a case by case basis
• No symptomatic brain metastases

PATIENT CHARACTERISTICS:

• Estimated life expectancy of at least 8 weeks
• Able to take oral medication
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No severe uncontrolled infection
• No unstable angina
• No myocardial infarction within the past month
• No uncontrolled inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis)
• No acute renal failure
• Bilirubin < 2 times upper limit of normal (ULN)
• Transaminases < 2 times ULN (5 times ULN if liver metastases are present)
• Creatinine < 5 times ULN
• No evidence of other significant laboratory finding or uncontrolled medical illness that would interfere with study treatment or results comparison or render the patient at high risk from treatment complications
• No other prior or current malignant disease likely to interfere with study treatment or comparisons

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy
• No prior biological anticancer therapy (e.g., gefitinib, thalidomide, or cetuximab)

• No prior palliative radiotherapy

  • Prior palliative radiotherapy to bone metastases allowed within the past 2 weeks
• No concurrent cyclooxygenase-2 inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erlotinib; Tarceva (OSI-774, erlotinib) PO 150mg daily	Drug: erlotinib hydrochloride; Tarceva (OSI-774, erlotinib) PO 150 mg daily; Other Names: Tarceva; OSI-774
Placebo Comparator: Matched placebo; Matched placebo PO daily	Drug: Matched placebo; Matched placebo PO daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	between date of randomisation and date of death from any cause

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival		from the date of randomisation to the date of first clinical evidence of progressive disease, or death.
Adverse events/Toxicity		during and for 28 days following Tarceva/placebo treatment
Quality of life	QL will be measured using the patient-completed EORTC-QLQ C30 and lung cancer module (LC 14). The primary QL outcome measures will be changes in overall QL and the five most commonly reported lung cancer symptoms (fatigue, breathlessness, cough, emotional functioning and pain).	between randomisation and 8 weeks.
Cost-effectiveness	Effectiveness will be estimated in terms of quality-adjusted life years. Mean survival will be calculated on the basis of observed mortality (i.e. a within-trial estimate) and by extrapolating the survival curves if some patients remain alive at the end of the trial.	from date of randomisation to death

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Roche Pharma AG; Cancer Research UK
• Investigators: Study Chair: Siow M Lee, MD, PhD, FRCP, University College London Hospitals

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (Estimate): January 11, 2006

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CDR0000457755; EudraCT number (Other Identifier: 2004-000729-31); ISRCTN (Registry Identifier: ISRCTN11460478); LLCG-TOPICAL; EU-20313; Cancer Research UK (CTAAC) (Other Grant/Funding Number: C1438/A4147); Roche AG Pharma (Other Grant/Funding Number: MO17591); UCL Trial Sponsor reference (Other Identifier: UCL/05/173)