Condition category
Cancer
Date applied
19/01/2004
Date assigned
25/02/2004
Last edited
29/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Not Applicable

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

Sponsor information

Organisation

University College London (UK)

Sponsor details

Gower Street
London
WC1E 6BT
United Kingdom

Sponsor type

University/education

Website

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

  1. 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.

  2. 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.

Additional files

Editorial Notes

29/03/2016: Publication reference added. On 12/06/2007 the overall trial end date was changed to 30/01/2009.