Clinical trial NCT00433498: Etoposide and Cisplatin or Carboplatin as First-Line Chemotherapy With or Without Pravastatin in Treating Patients With Small Cell Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
limited stage small cell lung cancer
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2007-02-12
Enrollment: 846
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Survival
timeFrame: Reported at death.
Secondary outcomes:
measure: Progression-free survival
timeFrame: Time until the date of disease progression
measure: Local progression-free survival (local control)
timeFrame: Time until the date of disease progression
measure: Response rate as measured by RECIST criteria after course 3
timeFrame: Post chemo cycle 3
measure: Toxicity as measured by CTCAE version 3.0
timeFrame: At every clinic visit or if serious, an SAE form shoudl be submitted
Other outcomes:
Locations:
city: Ashford-Kent
country: United Kingdom
facility: William Harvey Hospital
state: England
city: Aylesbury-Buckinghamshire
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Barnstaple
country: United Kingdom
facility: North Devon District Hospital
state: England
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Birmingham
country: United Kingdom
facility: City Hospital - Birmingham
state: England
city: Birmingham
country: United Kingdom
facility: Sandwell General Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Good Hope Hospital
state: England
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bradford
country: United Kingdom
facility: Bradford Royal Infirmary
state: England
city: Brighton
country: United Kingdom
facility: Sussex Cancer Centre at Royal Sussex County Hospital
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Chelmsford
country: United Kingdom
facility: Broomfield Hospital
state: England
city: Cheltenham
country: United Kingdom
facility: Gloucestershire Oncology Centre at Cheltenham General Hospital
state: England
city: Colchester
country: United Kingdom
facility: Essex County Hospital
state: England
city: Cosham
country: United Kingdom
facility: Queen Alexandra Hospital
state: England
city: Dartford Kent
country: United Kingdom
facility: Darent Valley Hospital
state: England
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
state: England
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: England
city: Durham
country: United Kingdom
facility: University Hospital of North Durham
state: England
city: Essex
country: United Kingdom
facility: Princess Alexandra Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Gloucester
country: United Kingdom
facility: Gloucestershire Royal Hospital
state: England
city: Grimsby
country: United Kingdom
facility: Diana Princess of Wales Hospital
state: England
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre at Royal Surrey County Hospital
state: England
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
state: England
city: Hereford
country: United Kingdom
facility: Hereford Hospitals
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Huddersfield, West Yorks
country: United Kingdom
facility: Huddersfield Royal Infirmary
state: England
city: Hull
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Ipswich
country: United Kingdom
facility: Ipswich Hospital
state: England
city: Keighley
country: United Kingdom
facility: Airedale General Hospital
state: England
city: King's Lynn
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cancer Research UK Clinical Centre at St. James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: Guy's Hospital
state: England
city: London
country: United Kingdom
facility: Queen Elizabeth Hospital - Woolwich
state: England
city: London
country: United Kingdom
facility: St. George's Hospital
state: England
city: London
country: United Kingdom
facility: Charing Cross Hospital
state: England
city: Luton
country: United Kingdom
facility: Luton and Dunstable Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
state: England
city: Margate
country: United Kingdom
facility: Queen Elizabeth The Queen Mother Hospital
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes General Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Freeman Hospital
state: England
city: Newport
country: United Kingdom
facility: St. Mary's Hospital
state: England
city: North Yorkshire
country: United Kingdom
facility: Friarage Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottinghamshire
country: United Kingdom
facility: King's Mills Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Orpington, Kent
country: United Kingdom
facility: Princess Royal University Hospital
state: England
city: Peterborough
country: United Kingdom
facility: Peterborough Hospitals Trust
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Scunthorpe
country: United Kingdom
facility: Scunthorpe General Hospital
state: England
city: Shrewsbury
country: United Kingdom
facility: Royal Shrewsbury Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: South Shields
country: United Kingdom
facility: South Tyneside District Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Stevenage
country: United Kingdom
facility: Lister Hospital
state: England
city: Torquay
country: United Kingdom
facility: Torbay Hospital
state: England
city: Walsall
country: United Kingdom
facility: Walsall Manor Hospital
state: England
city: Weston-super-Mare
country: United Kingdom
facility: Weston General Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Worcester
country: United Kingdom
facility: Worcestershire Royal Hospital
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Falkirk
country: United Kingdom
facility: Falkirk and District Royal Infirmary
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Cardiff
country: United Kingdom
facility: Llandough Hospital
state: Wales
city: Gwent
country: United Kingdom
facility: Nevill Hall Hospital
state: Wales
city: Haverfordwest
country: United Kingdom
facility: Withybush General Hospital
state: Wales
city: Newport Gwent
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
city: Swansea
country: United Kingdom
facility: Singleton Hospital
state: Wales
Study officials:
affiliation: Charing Cross Hospital
name: Michael J. Seckl, MD, PhD
role: STUDY_CHAIR
References: