Etoposide and Cisplatin or Carboplatin as First-Line Chemotherapy With or Without Pravastatin in Treating Patients With Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00433498
• Other study ID #: CDR0000531141
• Secondary ID: CRUK-LUNGSTAREU-
• Status: Completed
• Phase: Phase 3
• First received: February 8, 2007
• Last updated: December 1, 2014
• Start date: January 2007
• Est. completion date: November 2013

Study information

• Verified date: January 2013
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Health authority: UK: MHRA, UK: MREC
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as etoposide, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pravastatin may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by making tumor cells more sensitive to chemotherapy. It is not yet known whether etoposide and cisplatin or carboplatin are more effective with or without pravastatin in treating small cell lung cancer.

PURPOSE: This randomized phase III trial is studying etoposide and cisplatin or carboplatin to see how well they work when given as first-line chemotherapy together with pravastatin compared with first-line chemotherapy and a placebo in treating patients with small cell lung cancer.

Description:

OBJECTIVES:

Primary

• Compare the survival of patients with small cell lung cancer treated with etoposide phosphate in combination with cisplatin or carboplatin as first-line chemotherapy with vs without pravastatin.

Secondary

• Compare the progression-free survival of patients treated with these regimens.

• Compare the local progression-free survival (local control) of these patients.

• Compare the response rate in these patients.

• Compare the toxicity of these regimens in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease stage (limited stage vs extensive stage), ECOG performance status (0 or 1 vs 2 or 3), and participating site. Patients are randomized to 1 of 2 treatment arms.

All patients receive chemotherapy comprising cisplatin IV or carboplatin IV on day 1 and etoposide phosphate IV on days 1-3 or orally twice daily on days 2 and 3. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

• Arm I: Patients receive oral pravastatin daily beginning on day 1 of chemotherapy and continuing for up to 24 months.

• Arm II: Patients receive oral placebo daily beginning on day 1 of chemotherapy and continuing for up to 24 months.

Some patients may undergo blood and urine sample collection at baseline and periodically during and after study treatment. Samples are examined by genetic analysis, metabonomics and proteomics (to detect expression of RAS proteins, phospho-Erk, and other signals downstream of RAS), and cholesterol measurements.

After completion of study treatment, patients are followed every 2 months for 1 year and every 3 months thereafter.

Peer Reviewed and Funded or Endorsed by Cancer Research UK.

PROJECTED ACCRUAL: A total of 842 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 846
• Est. completion date: November 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

• Limited stage or extensive stage disease

• No mixed cell histology

• No symptomatic brain metastases that require immediate radiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3

• Life expectancy > 8 weeks

• Platelet count > 100,000/mm^3

• Hemoglobin = 9.0 g/dL

• Absolute neutrophil count > 1,500/mm^3

• Glomerular filtration rate = 50 mL/min

• Creatine kinase = 5 times upper limit of normal (ULN)

• Liver function tests (ALP, ALT/AST, and bilirubin) < 3 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 1 year after completion of chemotherapy/radiotherapy and for an additional 28 days after completion of pravastatin sodium

• Able to tolerate chemotherapy

• No evidence of significant medical condition or laboratory finding that, in the opinion of the investigator, would preclude study participation

• No family history of hypercholesterolemia

• No history of malignant tumor unless the patient has been without evidence of disease for = 3 years or tumor was a nonmelanoma skin tumor or early cervical cancer

PRIOR CONCURRENT THERAPY:

• More than 12 months since prior statin

• More than 4 weeks since prior fibrates (e.g., bezofibrate, gemfibrozil, or fenofibrate)

• No prior chemotherapy for this cancer

• No prior radiotherapy for this cancer unless to distant metastases (i.e., not within the thorax or thoracic/cervical spine area)

• No concurrent cyclosporine

• Concurrent radiotherapy allowed

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• carboplatin
Should be given according to local practice but suggested doses and schedules are provided in the protocol.
• cisplatin
Should be given according to local practice but suggested doses and schedules are provided in the protocol.
• etoposide phosphate
Day 1: given by IV, days 2 and 3 given by IV or oral. Dose should be given according to local practice but suggested doses and schedules are provided in the protocol.
• pravastatin sodium
40mg daily oral tablet taken for a maximum of 2 years

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	William Harvey Hospital	Ashford-Kent	England
United Kingdom	Stoke Mandeville Hospital	Aylesbury-Buckinghamshire	England
United Kingdom	North Devon District Hospital	Barnstaple	England
United Kingdom	Royal United Hospital	Bath	England
United Kingdom	Birmingham Heartlands Hospital	Birmingham	England
United Kingdom	City Hospital - Birmingham	Birmingham	England
United Kingdom	Good Hope Hospital	Birmingham	England
United Kingdom	Sandwell General Hospital	Birmingham	England
United Kingdom	Royal Bournemouth Hospital	Bournemouth	England
United Kingdom	Bradford Royal Infirmary	Bradford	England
United Kingdom	Sussex Cancer Centre at Royal Sussex County Hospital	Brighton	England
United Kingdom	Queen's Hospital	Burton-upon-Trent	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Kent and Canterbury Hospital	Canterbury	England
United Kingdom	Llandough Hospital	Cardiff	Wales
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Broomfield Hospital	Chelmsford	England
United Kingdom	Gloucestershire Oncology Centre at Cheltenham General Hospital	Cheltenham	England
United Kingdom	Essex County Hospital	Colchester	England
United Kingdom	Queen Alexandra Hospital	Cosham	England
United Kingdom	Darent Valley Hospital	Dartford Kent	England
United Kingdom	Royal Derby Hospital	Derby	England
United Kingdom	Dorset County Hospital	Dorchester	England
United Kingdom	University Hospital of North Durham	Durham	England
United Kingdom	Princess Alexandra Hospital	Essex	England
United Kingdom	Royal Devon and Exeter Hospital	Exeter	England
United Kingdom	Falkirk and District Royal Infirmary	Falkirk	Scotland
United Kingdom	Gloucestershire Royal Hospital	Gloucester	England
United Kingdom	Diana Princess of Wales Hospital	Grimsby	England
United Kingdom	St. Luke's Cancer Centre at Royal Surrey County Hospital	Guildford	England
United Kingdom	Nevill Hall Hospital	Gwent	Wales
United Kingdom	Harrogate District Hospital	Harrogate	England
United Kingdom	Withybush General Hospital	Haverfordwest	Wales
United Kingdom	Hereford Hospitals	Hereford	England
United Kingdom	Wycombe General Hospital	High Wycombe	England
United Kingdom	Huddersfield Royal Infirmary	Huddersfield, West Yorks	England
United Kingdom	Castle Hill Hospital	Hull	England
United Kingdom	Ipswich Hospital	Ipswich	England
United Kingdom	Airedale General Hospital	Keighley	England
United Kingdom	Queen Elizabeth Hospital	King's Lynn	England
United Kingdom	Cancer Research UK Clinical Centre at St. James's University Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Charing Cross Hospital	London	England
United Kingdom	Guy's Hospital	London	England
United Kingdom	Queen Elizabeth Hospital - Woolwich	London	England
United Kingdom	St. George's Hospital	London	England
United Kingdom	University College Hospital	London	England
United Kingdom	Luton and Dunstable Hospital	Luton	England
United Kingdom	Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Wythenshawe Hospital	Manchester	England
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England
United Kingdom	James Cook University Hospital	Middlesbrough	England
United Kingdom	Milton Keynes General Hospital	Milton Keynes	England
United Kingdom	Freeman Hospital	Newcastle-Upon-Tyne	England
United Kingdom	St. Mary's Hospital	Newport	England
United Kingdom	Royal Gwent Hospital	Newport Gwent	Wales
United Kingdom	Friarage Hospital	North Yorkshire	England
United Kingdom	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England
United Kingdom	Northampton General Hospital	Nottingham	England
United Kingdom	Nottingham City Hospital	Nottingham	England
United Kingdom	King's Mills Hospital	Nottinghamshire	England
United Kingdom	Princess Royal University Hospital	Orpington, Kent	England
United Kingdom	Peterborough Hospitals Trust	Peterborough	England
United Kingdom	Derriford Hospital	Plymouth	England
United Kingdom	Dorset Cancer Centre	Poole Dorset	England
United Kingdom	Berkshire Cancer Centre at Royal Berkshire Hospital	Reading	England
United Kingdom	Glan Clwyd Hospital	Rhyl, Denbighshire	Wales
United Kingdom	Salisbury District Hospital	Salisbury	England
United Kingdom	Scarborough General Hospital	Scarborough	England
United Kingdom	Scunthorpe General Hospital	Scunthorpe	England
United Kingdom	Royal Shrewsbury Hospital	Shrewsbury	England
United Kingdom	Wexham Park Hospital	Slough, Berkshire	England
United Kingdom	South Tyneside District Hospital	South Shields	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Lister Hospital	Stevenage	England
United Kingdom	Singleton Hospital	Swansea	Wales
United Kingdom	Torbay Hospital	Torquay	England
United Kingdom	Walsall Manor Hospital	Walsall	England
United Kingdom	Weston General Hospital	Weston-super-Mare	England
United Kingdom	New Cross Hospital	Wolverhampton	England
United Kingdom	Worcestershire Royal Hospital	Worcester	England
United Kingdom	Worthing Hospital	Worthing	England
United Kingdom	Yeovil District Hospital	Yeovil	England
United Kingdom	Cancer Care Centre at York Hospital	York	England

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		Reported at death.	No
Secondary	Progression-free survival		Time until the date of disease progression	No
Secondary	Local progression-free survival (local control)		Time until the date of disease progression	No
Secondary	Response rate as measured by RECIST criteria after course 3		Post chemo cycle 3	No
Secondary	Toxicity as measured by CTCAE version 3.0		At every clinic visit or if serious, an SAE form shoudl be submitted	Yes