A trial to see if a body protein called ERCC1 affects how people with advanced non small cell lung cancer respond to different types of chemotherapy

ISRCTN	ISRCTN02370070
DOI	https://doi.org/10.1186/ISRCTN02370070
EudraCT/CTIS number	2007-007639-17
ClinicalTrials.gov number	NCT00801736
Secondary identifying numbers	UCL/07/158

Submission date: 02/10/2008
Registration date: 12/11/2008
Last edited: 20/01/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

http://www.cancerhelp.org.uk/trials/trial-to-see-if-protein-ercc1-affects-how-people-with-advanced-non-small-cell-lung-cancer-respond-different-types-chemotherapy

Contact information

Dr Siow Ming Lee
Scientific

Consultant Medical Oncologist
The Department of Oncology
University College London Hospitals
1st Floor Central
250 Euston Road
London
NW1 2PG
United Kingdom

Study information

Study design	A multicentre, randomised, phase III trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	A multicentre, randomised, phase III trial of platinum-based chemotherapy versus non-platinum chemotherapy, after excision repair cross-complementation group 1 (ERCC1) protein stratification, in patients with advanced/metastatic non-small cell lung cancer (NSCLC)
Study acronym	ET Trial
Study hypothesis	The trial will have two main objectives: 1. To detect an improvement in survival for ERCC1 positive patients treated with a non-platinum chemotherapy compared to platinum-based treatment 2. To establish non-inferiority or improvement in survival for ERCC1 negative patients treated with a platinum-based chemotherapy compared to non-platinum treatment Secondary objectives: 1. To examine progression-free survival, response rate and quality of life between the two treatment regimens, according to ERCC1 status 2. To investigate whether the treatment effect differs according to: 2.1. Histology (squamous versus non-squamous) 2.2. Gender (males versus females) 2.3. Performance status 3. To undertake a cost-effectiveness analysis based on all patients, and according to ERCC1 status As of 22/02/2011 the anticipated end date for this trial has been updated from 30/11/2011 to 31/12/2014
Ethics approval(s)	Charing Cross Research Ethics Committee, 24/09/2008, ref: 08/H0711/45
Condition	Stage IIIb or IV non-small cell lung cancer (NSCLC)
Intervention	Patients are randomised to one of two treatment arms: Arm A: cisplatin/pemetrexed (cisplatin 75 mg/m2 over one hour/pemetrexed 500 mg/m2 over 10 minutes - intravenous [IV] administration) Arm B: paclitaxel/pemetrexed (paclitaxel 175 mg/m2 over three hours/pemetrexed 500 mg/m2 over 10 minutes - IV administration) Patients will receive up to six cycles of treatment; all patients are assessed with each cycle of chemotherapy. The first post-chemotherapy visit should be completed 3 - 4 weeks after last chemotherapy cycle. Assessments will then be monthly until one year from the date of first chemotherapy cycle, then two-monthly thereafter.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Pemetrexed, cisplatin, paclitaxel
Primary outcome measure	Survival: 1. To detect an improvement in survival for ERCC1 positive patients treated with a non-platinum chemotherapy compared to platinum-based treatment 2. To establish non-inferiority or improvement in survival for ERCC1 negative patients treated with a platinum-based chemotherapy compared to non-platinum treatment
Secondary outcome measures	1. Progression-free survival and response rate using RECIST 2. Quality of life - European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ C30) with additional lung cancer questions (LC 13) and EuroQol EQ-5D 3. Cost-effectiveness analysis - assessing trial medication use, management of adverse events, if other anti-cancer treatments used, assessing hospital admission episodes (in-patient nights) and day case visits, community-based support (e.g. visits to and from GP or nurse; time in hospice)
Overall study start date	22/11/2007
Overall study end date	31/12/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	1272
Participant inclusion criteria	1. Histologically confirmed NSCLC 2. Have a tissue biopsy available for sending to the central laboratory to determine ERCC1 status 3. Presentation with stage IIIb (not amenable to curative treatment) or IV disease staging scans must be no more than 28 days prior to randomisation. Patients with relapsed NSCLC must not have received prior chemotherapy or biological therapy (previous surgery or radical radiotherapy allowed). 4. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) 5. Either sex, at least 18 years of age 6. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1 7. Estimated life expectancy of at least 8 weeks 8. Adequate bone marrow function as evidenced by the following (assessed within 14 days of starting treatment): 8.1. Absolute neutrophil count (ANC) equal or more than 1.5 x 10^9/L 8.2. Platelet count equal or more than 75 x10^9/L 8.3. Haemoglobin equal or more than 9 g/dL 9. Adequate liver function as evidenced by the following (assessed within 14 days of starting treatment): 9.1. Total bilirubin equal or less than 1.5 x upper limit of normal (ULN) 9.2. Aspartate transaminase (AST) equal or less than 3 x ULN or equal or less than 5 x ULN is acceptable with liver metastases 9.3. Alanine transaminase (ALT) equal or less than 3 x ULN 10. Adequate renal function as evidenced by the following (assessed within 14 days of starting treatment): 10.1. Glomerular filtration rate (GFR) greater than 50 ml/min as measured by ethylenediaminetetraacetic acid (EDTA), or 10.2. GFR greater than 60 ml/min as measured by the Cockcroft and Gault formula 11. Previous palliative radiotherapy to non-target metastatic lesions is allowed (not in the 28 days prior to randomisation) 12. Patients with stable brain metastases will be allowed to enrol. Stable brain metastases being defined as no progression of brain metastases 28 days after treatment as documented by a computed tomography (CT) scan/magnetic resonance image (MRI) of the brain. Patients with incidentally discovered asymptomatic brain metastases may be enrolled and treated with trial chemotherapy without prior brain irradiation if deemed feasible by the treating physician. 13. Signed informed consent form 14. Use of effective contraception during, and for 6 months after trial treatment by patients of reproductive potential and partners of reproductive potential. Patients who receive aprepitant (anti-emetic) must be willing to use an alternative or back-up method to hormonal contraceptives as aprepitant may reduce their efficacy. 15. Female patients with childbearing potential must have a negative serum pregnancy test prior to randomisation
Participant exclusion criteria	1. Cytologically or clinically diagnosed NSCLC 2. Evidence of significant medical condition or laboratory finding which, in the opinion of the treating physician or chief investigator, makes it undesirable for the patient to participate in the trial, e.g.: 2.1. Congestive heart failure 2.2. Myocardial infarction within 6 months 2.3. Significant neurological or psychiatric disorders that would impact trial participation 2.4. Infection requiring intravenous (I.V.) antibiotics 2.5. Tuberculosis with ongoing therapy at trial entry 2.6. Superior vena cava syndrome, except if controlled with radiation 2.7. Active peptic ulcer disease 2.8. Uncontrolled diabetes mellitus 2.9. Any contraindication to high dose corticosteroid therapy such as herpes simplex, herpes zoster, hepatitis, or other disease 3. Presence of uncontrolled brain or leptomeningeal metastases thought to require immediate radiotherapy 4. Presence of clinically significant third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to trial entry 5. Unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) 6. Unable or unwilling to take vitamin B12 and folic acid 7. A history of prior malignant tumour, unless the patient has been without evidence of disease for at least 3 years or the tumour was a non-melanoma skin tumour or early cervical cancer 8. Pregnant or lactating women 9. Inability to comply with protocol or trial procedures
Recruitment start date	02/10/2009
Recruitment end date	24/07/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University College Hospital

235 Euston Road
Fitzrovia
London
NW1 2PG
United Kingdom

Sponsor information

University College London (UK)
University/education

Gower Street
London
WC1E 6BT
England
United Kingdom

Website	http://www.ucl.ac.uk/
"ROR"	https://ror.org/02jx3x895

Funders

Funder type

Industry

Eli Lilly and Company
Government organisation / For-profit companies (industry)

Alternative name(s): Lilly, Eli Lilly & Company, Eli Lilly & Co., Eli Lilly And Co
Location: United States of America

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
Publication and dissemination plan	Planned publication in a peer reviewed journal.
IPD sharing plan	The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results				No	No
Results article	results	01/02/2017		Yes	No
Results article	results	01/10/2019	10/09/2019	Yes	No
Plain English results			20/01/2022	No	Yes

Editorial Notes

20/01/2022: Publication reference added.
19/03/2020: EudraCT number added. Added EudraCT link to basic results (scientific).
14/02/2020: ClinicalTrials.gov number added.
10/09/2019: Publication reference added.
14/01/2019: Publication details added.
30/11/2016: The following changes have been made to the record:
1. The overall trial dates have been updated from 01/12/2008 - 31/12/2014 to 22/11/2007 - 31/12/2017 and the recruitment dates have been updated from 01/12/2008 - 31/12/2014 to 02/10/2009 - 24/07/2013.
2. The availability of participant-level data, public title and ethics approval reference number have been added.
3. Publication reference added.
18/11/2016: No publications found in PubMed, verifying study status with principal investigator.