Plain English Summary
Trial website
Contact information
Type
Scientific
Primary contact
Dr Siow-Ming Lee
ORCID ID
Contact details
Consultant Medical Oncologist
Meyerstein Institute of Oncology
Middlesex and UCL Hospitals
Mortimer Street
London
W1N 8AA
United Kingdom
+44 (0)20 7380 9091
sm.lee@uclh.org
Additional identifiers
EudraCT number
2004-000729-31
ClinicalTrials.gov number
NCT00275132
Protocol/serial number
N/A
Study information
Scientific title
A randomised, placebo-controlled trial of Tarceva (OSI-774, erlotinib) in patients with advanced non-small cell lung cancer unsuitable for chemotherapy
Acronym
TOPICAL
Study hypothesis
Erlotinib may stop the growth of tumour 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 (NSCLC).
Ethics approval
Multicentre Research Ethics Committee (MREC), 04/05/2004, ref: 04/6/032
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Non-small cell lung cancer (NSCLC)
Intervention
Patients are randomised to one of two treatment arms with 1:1 randomisation:
Arm 1: Tarceva (OSI-774, erlotinib) PO (by mouth) 150 mg daily up to 24 months.
Arm 2: Matched placebo PO daily up to 24 months
Intervention type
Drug
Phase
Phase III
Drug names
Erlotinib
Primary outcome measures
To compare the effect on survival of Tarceva compared to placebo in patients with advanced NSCLC not suitable for chemotherapy.
Secondary outcome measures
1. Progression free survival
2. Toxicity
3. Response rate
4. Quality of life
5. Cost-effectiveness
Overall trial start date
01/04/2005
Overall trial end date
31/01/2008
Reason abandoned
Eligibility
Participant inclusion criteria
1. Diagnosis within 62 days prior to randomisation (this criteria was added on the 12th June 2007)
2. Histologically or cytologically confirmed NSCLC
3. Advanced disease NSCLC (stage IIIb or IV)
4. Chemotherapy-naive patients
5. Patients considered unsuitable for chemotherapy, for example:*
5.1. Eastern Cooperative Oncology Group (ECOG) performance status two or three
5.2. ECOG performance status zero or one with a calculated creatinine clearance less than or equal to 60 ml/min (Cockroft formula)
6. Aged 18 years or over
7. Estimated life expectancy of at least 8 weeks
8. Able to take oral medication
9. Using effective contraception if of reproductive potential (women of child bearing potential must have a negative pregnancy test performed by a healthcare professional prior to randomisation)
10. Willing and able to give informed consent
11. Willing to participate in the biological study
* examples given do not imply that all such patients are unsuitable for chemotherapy - patients should be considered individually
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
664
Participant exclusion criteria
1. Previous treatment with any biological anti-cancer therapy (e.g. Iressa, thalidomide, cetuximab)
2. Prior chemotherapy
3. Prior palliative radiotherapy (except to bone metastases, within the last 2 weeks)
4. Pregnant or lactating women
5. Evidence of other significant laboratory finding or concurrent uncontrolled medical illness which in the opinion of the investigator would interfere with protocol treatment or results comparison or render the subject at high risk from treatment complications. Examples include:
5.1. Severe uncontrolled infection
5.2. Cardiovascular: unstable angina, myocardial infarction within 1 month
5.3. Gastro-intestinal: uncontrolled inflammatory bowel disease (e.g. Crohn's or ulcerative colitis)
5.4. Hepatic:
5.4.1. Serum bilirubin more than or equal to 2 x Upper Limit of Normal (ULN)
5.4.2. Serum transaminases more than or equal to 2 x ULN in the absence of liver metastases, or more than or equal to 5 x ULN with liver metastases
5.5. Renal:
5.5.1. Acute renal failure
5.5.2. Serum creatinine more than or equal to 5 x ULN
6. Other previous or current malignant disease likely to interfere with protocol treatment or comparisons
7. Symptomatic brain metastases
8. Current treatment with Cox II inhibitor
Recruitment start date
01/04/2005
Recruitment end date
31/01/2008
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Middlesex and UCL Hospitals
London
W1N 8AA
United Kingdom
Funders
Funder type
Charity
Funder name
Cancer Research UK (CRUK) (UK) (ref: C1438/A4147)
Alternative name(s)
CRUK
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
London Lung Cancer Group (UK) (Charity no. 1074994)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/23078958
2015 cost-effectiveness results in: http://www.ncbi.nlm.nih.gov/pubmed/26137881
Publication citations
-
Results
Lee SM, Khan I, Upadhyay S, Lewanski C, Falk S, Skailes G, Marshall E, Woll PJ, Hatton M, Lal R, Jones R, Toy E, Chao D, Middleton G, Bulley S, Ngai Y, Rudd R, Hackshaw A, Boshoff C, First-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy (TOPICAL): a double-blind, placebo-controlled, phase 3 trial., Lancet Oncol., 2012, 13, 11, 1161-1170, doi: 10.1016/S1470-2045(12)70412-6.
-
Results
Cost-effectiveness of first-line erlotinib in patients with advanced non-small-cell lung cancer unsuitable for chemotherapy, BMJ Open, 2015 , 5, 7, e006733, doi: 10.1136/bmjopen-2014-006733.