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

NCT ID: NCT00433498

Last Updated: 2014-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

846 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2013-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Carboplatin/cisplatin and Etoposide with Pravastatin

Group Type EXPERIMENTAL

carboplatin

Intervention Type DRUG

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

cisplatin

Intervention Type DRUG

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

etoposide phosphate

Intervention Type DRUG

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

Intervention Type DRUG

40mg daily oral tablet taken for a maximum of 2 years

Carboplatin/cisplatin and Etoposide with Placebo

Group Type PLACEBO_COMPARATOR

carboplatin

Intervention Type DRUG

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

cisplatin

Intervention Type DRUG

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

etoposide phosphate

Intervention Type DRUG

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.

Interventions

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carboplatin

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

Intervention Type DRUG

cisplatin

Should be given according to local practice but suggested doses and schedules are provided in the protocol.

Intervention Type DRUG

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.

Intervention Type DRUG

pravastatin sodium

40mg daily oral tablet taken for a maximum of 2 years

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University College, London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael J. Seckl, MD, PhD

Role: STUDY_CHAIR

Charing Cross Hospital

Locations

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William Harvey Hospital

Ashford-Kent, England, United Kingdom

Site Status

Stoke Mandeville Hospital

Aylesbury-Buckinghamshire, England, United Kingdom

Site Status

North Devon District Hospital

Barnstaple, England, United Kingdom

Site Status

Royal United Hospital

Bath, England, United Kingdom

Site Status

City Hospital - Birmingham

Birmingham, England, United Kingdom

Site Status

Sandwell General Hospital

Birmingham, England, United Kingdom

Site Status

Good Hope Hospital

Birmingham, England, United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, England, United Kingdom

Site Status

Royal Bournemouth Hospital

Bournemouth, England, United Kingdom

Site Status

Bradford Royal Infirmary

Bradford, England, United Kingdom

Site Status

Sussex Cancer Centre at Royal Sussex County Hospital

Brighton, England, United Kingdom

Site Status

Queen's Hospital

Burton-on-Trent, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Kent and Canterbury Hospital

Canterbury, England, United Kingdom

Site Status

Broomfield Hospital

Chelmsford, England, United Kingdom

Site Status

Gloucestershire Oncology Centre at Cheltenham General Hospital

Cheltenham, England, United Kingdom

Site Status

Essex County Hospital

Colchester, England, United Kingdom

Site Status

Queen Alexandra Hospital

Cosham, England, United Kingdom

Site Status

Darent Valley Hospital

Dartford Kent, England, United Kingdom

Site Status

Royal Derby Hospital

Derby, England, United Kingdom

Site Status

Dorset County Hospital

Dorchester, England, United Kingdom

Site Status

University Hospital of North Durham

Durham, England, United Kingdom

Site Status

Princess Alexandra Hospital

Essex, England, United Kingdom

Site Status

Royal Devon and Exeter Hospital

Exeter, England, United Kingdom

Site Status

Gloucestershire Royal Hospital

Gloucester, England, United Kingdom

Site Status

Diana Princess of Wales Hospital

Grimsby, England, United Kingdom

Site Status

St. Luke's Cancer Centre at Royal Surrey County Hospital

Guildford, England, United Kingdom

Site Status

Harrogate District Hospital

Harrogate, England, United Kingdom

Site Status

Hereford Hospitals

Hereford, England, United Kingdom

Site Status

Wycombe General Hospital

High Wycombe, England, United Kingdom

Site Status

Huddersfield Royal Infirmary

Huddersfield, West Yorks, England, United Kingdom

Site Status

Castle Hill Hospital

Hull, England, United Kingdom

Site Status

Ipswich Hospital

Ipswich, England, United Kingdom

Site Status

Airedale General Hospital

Keighley, England, United Kingdom

Site Status

Queen Elizabeth Hospital

Kings Lynn, England, United Kingdom

Site Status

Cancer Research UK Clinical Centre at St. James's University Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

University College Hospital

London, England, United Kingdom

Site Status

Guy's Hospital

London, England, United Kingdom

Site Status

Queen Elizabeth Hospital - Woolwich

London, England, United Kingdom

Site Status

St. George's Hospital

London, England, United Kingdom

Site Status

Charing Cross Hospital

London, England, United Kingdom

Site Status

Luton and Dunstable Hospital

Luton, England, United Kingdom

Site Status

Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Christie Hospital

Manchester, England, United Kingdom

Site Status

Wythenshawe Hospital

Manchester, England, United Kingdom

Site Status

Queen Elizabeth The Queen Mother Hospital

Margate, England, United Kingdom

Site Status

James Cook University Hospital

Middlesbrough, England, United Kingdom

Site Status

Milton Keynes General Hospital

Milton Keynes, England, United Kingdom

Site Status

Freeman Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

St. Mary's Hospital

Newport, England, United Kingdom

Site Status

Friarage Hospital

North Yorks, England, United Kingdom

Site Status

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Site Status

Northampton General Hospital

Nottingham, England, United Kingdom

Site Status

Nottingham City Hospital

Nottingham, England, United Kingdom

Site Status

King's Mills Hospital

Nottinghamshire, England, United Kingdom

Site Status

Princess Royal University Hospital

Orpington, Kent, England, United Kingdom

Site Status

Peterborough Hospitals Trust

Peterborough, England, United Kingdom

Site Status

Derriford Hospital

Plymouth, England, United Kingdom

Site Status

Dorset Cancer Centre

Poole Dorset, England, United Kingdom

Site Status

Berkshire Cancer Centre at Royal Berkshire Hospital

Reading, England, United Kingdom

Site Status

Salisbury District Hospital

Salisbury, England, United Kingdom

Site Status

Scarborough General Hospital

Scarborough, England, United Kingdom

Site Status

Scunthorpe General Hospital

Scunthorpe, England, United Kingdom

Site Status

Royal Shrewsbury Hospital

Shrewsbury, England, United Kingdom

Site Status

Wexham Park Hospital

Slough, Berkshire, England, United Kingdom

Site Status

South Tyneside District Hospital

South Shields, England, United Kingdom

Site Status

Southampton General Hospital

Southampton, England, United Kingdom

Site Status

Lister Hospital

Stevenage, England, United Kingdom

Site Status

Torbay Hospital

Torquay, England, United Kingdom

Site Status

Walsall Manor Hospital

Walsall, England, United Kingdom

Site Status

Weston General Hospital

Weston-super-Mare, England, United Kingdom

Site Status

New Cross Hospital

Wolverhampton, England, United Kingdom

Site Status

Worcestershire Royal Hospital

Worcester, England, United Kingdom

Site Status

Worthing Hospital

Worthing, England, United Kingdom

Site Status

Yeovil District Hospital

Yeovil, England, United Kingdom

Site Status

Cancer Care Centre at York Hospital

York, England, United Kingdom

Site Status

Aberdeen Royal Infirmary

Aberdeen, Scotland, United Kingdom

Site Status

Falkirk and District Royal Infirmary

Falkirk, Scotland, United Kingdom

Site Status

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Llandough Hospital

Cardiff, Wales, United Kingdom

Site Status

Nevill Hall Hospital

Gwent, Wales, United Kingdom

Site Status

Withybush General Hospital

Haverfordwest, Wales, United Kingdom

Site Status

Royal Gwent Hospital

Newport Gwent, Wales, United Kingdom

Site Status

Glan Clwyd Hospital

Rhyl, Denbighshire, Wales, United Kingdom

Site Status

Singleton Hospital

Swansea, Wales, United Kingdom

Site Status

Countries

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United Kingdom

Other Identifiers

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CRUK-LUNGSTAR

Identifier Type: -

Identifier Source: secondary_id

EU-20649

Identifier Type: -

Identifier Source: secondary_id

ISRCTN56306957

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2005-005821-71

Identifier Type: -

Identifier Source: secondary_id

UCL-BRD/05/129

Identifier Type: -

Identifier Source: secondary_id

MREC-06-MRE10-28

Identifier Type: -

Identifier Source: secondary_id

CTA-20363-0215-001

Identifier Type: -

Identifier Source: secondary_id

CTAAC-C1312-A5335

Identifier Type: -

Identifier Source: secondary_id

CTAAC-C1312-A12462

Identifier Type: -

Identifier Source: secondary_id

CDR0000531141

Identifier Type: -

Identifier Source: org_study_id