Clinical trial NCT00316927: Dexamethasone, Aspirin, and Diethylstilbestrol in Treating Patients With Locally Advanced or Metastatic Prostate Cancer
Official title: A Randomized Phase III Trial of Dexamethasone and Aspirin (DA) Versus Dexamethasone, Diethylstilbestrol and Aspirin (DAS) in Locally Advanced or Metastatic Cancer of the Prostate - Immediate Versus Deferred Diethylstilbestrol
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-04-21
Enrollment: 260
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving dexamethasone together with aspirin and diethylstilbestrol may be effective in lowering prostate-specific antigen levels and may slow or stop the growth of prostate cancer. It is not yet known which schedule of dexamethasone, aspirin, and diethylstilbestrol is more effective in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying dexamethasone and aspirin when given together with two different schedules of diethylstilbestrol to compare how well they work in treating patients with locally advanced or metastatic prostate cancer.

Detailed description: OBJECTIVES:

Primary

* Compare the prostate-specific antigen (PSA) response in patients with locally advanced or metastatic prostate cancer treated with dexamethasone and aspirin with delayed vs immediate diethylstilbestrol.

Secondary

* Compare the overall response rate in patients treated with these regimens.
* Compare the quality of life of patients treated with these regimens.
* Compare the progression-free and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to ECOG performance status (0 vs 1-3), prostate-specific antigen (PSA) response to prior therapy (PSA normalization vs inability to normalize), and bone scan (positive vs negative for bony metastases). Patients are randomized to 1 of 2 treatment arms.

* Arm I (deferred diethylstilbestrol): Patients receive oral dexamethasone and oral acetylsalicyclic acid once daily (DA). Subsequent to treatment failure with DA, patients continue to receive DA as before in addition to oral diethylstilbestrol once daily (DAS). Treatment with DAS continues in the absence of disease progression or unacceptable toxicity.
* Arm II (immediate diethylstilbestrol): Patients receive oral dexamethasone, oral acetylsalicyclic acid, and oral diethylstilbestrol once daily (DAS). Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is evaluated monthly during study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 260 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of adenocarcinoma of the prostate

  * Elevated prostate-specific antigen (PSA)
* Failed previous treatments, including gonadatropan regulatory hormone analogue therapy, radiotherapy, surgery, or any combination of these
* Biochemically castrate (testosterone \< 1 nmol/L) at baseline

PATIENT CHARACTERISTICS:

* Life expectancy ≥ 3 months
* ECOG performance status 0-3
* WBC ≥ 3,000/mm\^3
* Absolute neutrophil count (neutrophils and bands) ≥ 2,000/mm\^3
* Platelet count ≥ 50,000/mm\^3
* Bilirubin ≤ 2 times upper limit of normal (ULN)
* AST or ALT ≤ 3 times ULN
* Creatinine ≤ 1.5 times ULN
* Able to swallow tablets
* No other malignancy within the past 3 years except basal cell skin cancer
* No previous thromboembolic disease, including stroke, venous or arterial thrombosis, and myocardial infarction with ongoing angina pectoris

  * Prior uncomplicated myocardial infarction allowed
* No diabetes mellitus if treatment titration is thought to be difficult or inappropriate
* No active gastric or duodenal ulcer

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Prior concurrent bisphosphonates allowed
* No concurrent investigational agents or participation in another investigational drug study
* No other concurrent antineoplastic therapy, including new estrogen therapy, radiation therapy, or PC-SPES
* No other concurrent corticosteroids (e.g., dexamethasone for nausea or vomiting) except those prescribed in the study regimen

Primary outcomes:
measure: Prostate-specific antigen (PSA) response
Secondary outcomes:
measure: Overall response
measure: Quality of life
measure: Progression-free and overall survival
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Burnley
country: United Kingdom
facility: Burnley General Hospital
state: England
city: Canterbury
country: United Kingdom
facility: Kent and Canterbury Hospital
state: England
city: Eastbourne
country: United Kingdom
facility: Eastbourne District General Hospital
state: England
city: London
country: United Kingdom
facility: Whipps Cross Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Chelsea Westminster Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital
state: England
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes General Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Torquay Devon
country: United Kingdom
facility: Torbay Hospital
state: England
city: Weston-super-Mare
country: United Kingdom
facility: Weston General Hospital
state: England
city: Worthing
country: United Kingdom
facility: Worthing Hospital
state: England
city: York
country: United Kingdom
facility: Cancer Care Centre at York Hospital
state: England
Study officials:
affiliation: St. Bartholomew's Hospital
name: Jonathan Shamash, MD, FRCP
role: STUDY_CHAIR
References:
citation: Shamash J, Powles T, Sarker SJ, Protheroe A, Mithal N, Mills R, Beard R, Wilson P, Tranter N, O'Brien N, McFaul S, Oliver T. A multi-centre randomised phase III trial of Dexamethasone vs Dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred Diethylstilbestrol. Br J Cancer. 2011 Feb 15;104(4):620-8. doi: 10.1038/bjc.2011.7. Epub 2011 Feb 1.