Clinical trial NCT00744497: Randomized Study Comparing Docetaxel Plus Dasatinib to Docetaxel Plus Placebo in Castration-resistant Prostate Cancer
Official title: A Randomized Double-Blind Phase 3 Trial Comparing Docetaxel Combined With Dasatinib to Docetaxel Combined With Placebo in Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostatic Neoplasms
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-09-01
Enrollment: 1930
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether survival can be prolonged in patients with castration-resistant prostate cancer who receive dasatinib with docetaxel and prednisone.


Eligibility criteria: Inclusion Criteria:

* History of histologically diagnosed prostate cancer
* Evidence of metastatic disease by any 1 of the following: computed tomography scan, magnetic resonance imaging, bone scan, or skeletal survey
* Evidence of progression, as defined by 1 of the following: rising prostate specific antigen levels at least 1 week apart with the final value being \>=2 ng/mL; progression of measurable nodal or visceral disease, with nodal lesions \>=20 mm and visceral lesions measurable per response evaluation criteria for solid tumors (Response Evaluation in Solid Tumors, version 1); 2 or more lesions appearing on bone scan compared with previous scan; or local recurrence in the prostate or prostate bed
* Maintaining castrate status: Participants who have not undergone surgical orchiectomy should have received and continue on medical therapies, such as gonadotropin releasing hormone analogs, to maintain castrate levels of serum testosterone \<=50 ng/dL
* Eastern Cooperative Oncology Group Performance Status of 0 to 2
* At least 4 weeks since an investigational agent prior to starting study therapy
* At least 8 weeks since radioisotope therapy prior to starting study therapy
* Recovery from any local therapy including surgery or radiation/radiotherapy for a minimum of 7 days prior to starting study therapy
* Required initial laboratory values: white blood cell count \>=3,000/mm\^3; absolute neutrophil count \>=1,500/mm\^3; platelet count \>=100,000/mm\^3; creatinine level \<=1.5\*upper limit of normal (ULN); bilirubin \<=ULN; aspartate aminotransferase \<=2.5\*ULN; alanine aminotransferase \<=2.5\*ULN.

Exclusion Criteria:

* Symptomatic brain metastases or leptomeningeal metastases
* Clinically significant cardiovascular disease, including myocardial infarction; ventricular tachyarrhythmia within 6 months; prolonged QTc \>450 msec; ejection fraction \<40%; or major conduction abnormality, unless a cardiac pacemaker is present
* Pleural or pericardial effusion of any Common Terminology Criteria (CTC) grade
* Peripheral neuropathy CTC Grade \>=2
* Currently active second malignancy other than nonmelanoma skin cancers. Participants are not considered to have a currently active malignancy if they have completed therapy and are now considered (by their physician) to be at less than 30% risk for relapse
* Uncontrolled intercurrent illness including ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* HIV infection-positive patients receiving combination antiretroviral therapy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to the investigational agents
* Receipt of any other investigational agents for the treatment of prostate cancer
* Prior cytotoxic chemotherapy in the metastatic setting, with the exception of estramustine
* Patients may continue on a daily multivitamin but must discontinue all other herbal, alternative, and food supplements before enrollment
* Ketoconazole must be discontinued 4 weeks prior to starting study therapy
* Antiandrogens must be discontinued prior to starting study therapy. Patients with a history of response to an antiandrogen and subsequent progression while on that antiandrogen should be assessed for antiandrogen withdrawal response for 4 weeks. Observation for antiandrogen withdrawal response is not necessary for those who have never responded to antiandrogens
* Bisphosphonates must not be initiated within 28 days prior to starting study therapy
* QT prolonging agents strongly associated with torsade de pointes.

Primary outcomes:
measure: Overall Survival: Time From Randomization to Date of Death
timeFrame: From randomization to death or date of last contact (maximum reached: 45 months)
Secondary outcomes:
measure: Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing)
measure: Time to First Skeletal-related Event (SRE)
timeFrame: From day of randomization to date of first SRE or to last SRE assessment, if subsequent cancer therapy begun or no SRE (maximum reached: 42 months)
measure: Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline
timeFrame: At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing)
measure: Progression-free Survival (PFS)
timeFrame: From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months)
measure: Time to Prostate Specific Antigen (PSA) Progression
timeFrame: From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months)
measure: Percentage of Participants With a Reduction in Pain Intensity From Baseline
timeFrame: At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing)
Other outcomes:
measure: Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths
timeFrame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days
measure: Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest
timeFrame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days
measure: Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology
timeFrame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle) and at end of treatment. If docetaxel is discontinued, every other cycle.
measure: Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes
timeFrame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.
measure: Number of Participants With Abnormal Results in Urinalysis
timeFrame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.
measure: Number of Participants by Maximal On-study Fridericia-corrected QTc Interval
timeFrame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing
measure: Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval
timeFrame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing
measure: Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study
timeFrame: At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated
Locations:
city: Mobile
country: United States
facility: University Of South Alabama / Mitchell Cancer Institute
state: Alabama
city: Mobile
country: United States
facility: Southern Cancer Center
state: Alabama
city: Anchorage
country: United States
facility: Alaska Clinical Research Center, Llc
state: Alaska
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Corona
country: United States
facility: Compassionate Cancer Care Medical Group, Inc.
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group Inc
state: California
city: San Diego
country: United States
facility: Sharp Clinical Oncology Research
state: California
city: San Diego
country: United States
facility: Va San Diego Healthcare System
state: California
city: Santa Ana
country: United States
facility: Edward Alexson, Md, Inc.
state: California
city: Middletown
country: United States
facility: Connecticut Oncology Group
state: Connecticut
city: West Haven
country: United States
facility: Va Connecticut Healthcare System
state: Connecticut
city: Lawrenceville
country: United States
facility: Gwinnett Hospital System Inc.
state: Georgia
city: Chicago
country: United States
facility: University Of Chicago
state: Illinois
city: Zion
country: United States
facility: Midwestern Regional Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology And Hematology Inc
state: Indiana
city: Wichita
country: United States
facility: Cancer Center Of Kansas
state: Kansas
city: Scarborough
country: United States
facility: Maine Center For Cancer Medicine
state: Maine
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Jackson
country: United States
facility: Jackson Oncology Associates, Pllc
state: Mississippi
city: Tupelo
country: United States
facility: North Mississippi Hematology And Oncology Associates, Ltd
state: Mississippi
city: Albany
country: United States
facility: New York Oncology Hematology, Pc
state: New York
city: Albany
country: United States
facility: New York Oncology Hematology, Pc
state: New York
city: Albany
country: United States
facility: Samuel S. Stratton Vamc
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-salem
country: United States
facility: Piedmont Hematology Oncology Associates, Pllc
state: North Carolina
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Columbus
country: United States
facility: Mid Ohio Oncology/Hematology, Inc,Dba
state: Ohio
city: Portland
country: United States
facility: Providence Portland Med Ctr
state: Oregon
city: Langhorne
country: United States
facility: Regional Hemetology Oncology, Pc
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Upmc Cancer Pavilion
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Va Pittsburgh Healthcare System
state: Pennsylvania
city: Upland
country: United States
facility: Associates In Hematology & Oncology, P.C.
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Greenville
country: United States
facility: Cancer Centers Of The Carolinas
state: South Carolina
city: Memphis
country: United States
facility: Boston Baskin Cancer Foundation
state: Tennessee
city: Corpus Christi
country: United States
facility: Cancer Specialists Of South Texas, Pa
state: Texas
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
city: Lacey
country: United States
facility: Providence Regional Cancer System
state: Washington
city: Seattle
country: United States
facility: University Of Washington
state: Washington
city: Madison
country: United States
facility: Dean Hematology And Oncology Clinic
state: Wisconsin
city: Caba
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Capital Federal
country: Argentina
facility: Local Institution
state: Buenos Aires
city: La Plata
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Ramos Mejia
country: Argentina
facility: Local Institution
state: Buenos Aires
city: Cipolletti
country: Argentina
facility: Local Institution
state: Rio Negro
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: Rosario
country: Argentina
facility: Local Institution
state: Santa Fe
city: San Miguel De Tucuman
country: Argentina
facility: Local Institution
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Cordaba
country: Argentina
facility: Local Institution
city: Coffs Harbour
country: Australia
facility: Local Institution
state: New South Wales
city: Lismore
country: Australia
facility: Local Institution
state: New South Wales
city: Port Macquarie
country: Australia
facility: Local Institution
state: New South Wales
city: Sydney
country: Australia
facility: Local Institution
state: New South Wales
city: Douglas
country: Australia
facility: Local Institution
state: Queensland
city: Milton
country: Australia
facility: Local Institution
state: Queensland
city: Kurralta Park
country: Australia
facility: Local Institution
state: South Australia
city: Hobart
country: Australia
facility: Local Institution
state: Tasmania
city: Frankston
country: Australia
facility: Local Institution
state: Victoria
city: Ringwood
country: Australia
facility: Local Institution
state: Victoria
city: Fremantle
country: Australia
facility: Local Institution
state: Western Australia
city: Salvador
country: Brazil
facility: Local Institution
state: Bahia
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Jau
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Santo Andre
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Abbottsford
country: Canada
facility: Local Institution
state: British Columbia
city: Moncton
country: Canada
facility: Local Institution
state: New Brunswick
city: Ottawa
country: Canada
facility: Local Institution
state: Ontario
city: Owen Sound
country: Canada
facility: Local Institution
state: Ontario
city: Sudbury
country: Canada
facility: Local Institution
state: Ontario
city: Thunder Bay
country: Canada
facility: Local Institution
state: Ontario
city: Greenfield Park
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Rimouski
country: Canada
facility: Local Institution
state: Quebec
city: Sherbrooke
country: Canada
facility: Local Institution
state: Quebec
city: Regina
country: Canada
facility: Local Institution
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Local Institution
state: Saskatchewan
city: Brno
country: Czech Republic
facility: Local Institution
city: Hradec Kralove
country: Czech Republic
facility: Local Institution
city: Praha 2
country: Czech Republic
facility: Local Institution
city: Praha 8
country: Czech Republic
facility: Local Institution
city: Turku
country: Finland
facility: Local Institution
city: Vaasa
country: Finland
facility: Local Institution
city: Avignon
country: France
facility: Local Institution
city: Besancon Cedex
country: France
facility: Local Institution
city: Caen
country: France
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: St Genis Laval
country: France
facility: Local Institution
city: Strasbourg
country: France
facility: Local Institution
city: Aachen
country: Germany
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Erlangen
country: Germany
facility: Local Institution
city: Essen
country: Germany
facility: Local Institution
city: Kirchheim
country: Germany
facility: Local Institution
city: Markkleeberg
country: Germany
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Budapest
country: Hungary
facility: Local Institution
city: Kecskemet
country: Hungary
facility: Local Institution
city: Zalaegerszeg
country: Hungary
facility: Local Institution
city: Trivandrum
country: India
facility: Local Institution
state: Kerala
city: Mumbai
country: India
facility: Local Institution
state: Maharashtra
city: Pune
country: India
facility: Local Institution
state: Maharashtra
city: Pune
country: India
facility: Local Institution
state: Maharashtra
city: Ahmedabad
country: India
facility: Local Institution
city: Jaipur
country: India
facility: Local Institution
city: Kolkata
country: India
facility: Local Institution
city: Kolkatta
country: India
facility: Local Institution
city: Dublin 7
country: Ireland
facility: Local Institution
state: Dublin
city: Tallaght
country: Ireland
facility: Local Institution
state: Dublin
city: Cork
country: Ireland
facility: Local Institution
city: Dublin
country: Ireland
facility: Local Institution
city: Arezzo
country: Italy
facility: Local Institution
city: Genova
country: Italy
facility: Local Institution
city: Lecce
country: Italy
facility: Local Institution
city: Milan
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Perugia
country: Italy
facility: Local Institution
city: Roma
country: Italy
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Tijuana
country: Mexico
facility: Local Institution
state: Baja California
city: Df
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Mexico D.f.
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Tlalpan
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Tlalpan
country: Mexico
facility: Local Institution
state: Distrito Federal
city: Huixquilucan
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Toluca
country: Mexico
facility: Local Institution
state: Estado De Mexico
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Zapopan
country: Mexico
facility: Local Institution
state: Jalisco
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Mexico
country: Mexico
facility: Local Institution
state: Queretaro
city: Stavanger
country: Norway
facility: Local Institution
city: Callao
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Lima
country: Peru
facility: Local Institution
city: Bialystok
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Warszawa
country: Poland
facility: Local Institution
city: Baia Mare
country: Romania
facility: Local Institution
city: Cluj Napoca
country: Romania
facility: Local Institution
city: Timisoara, Timis
country: Romania
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: St Petersburg
country: Russian Federation
facility: Local Institution
city: Bloemfontein
country: South Africa
facility: Local Institution
state: Free State
city: Pretoria
country: South Africa
facility: Local Institution
state: Gauteng
city: Saxonwold
country: South Africa
facility: Local Institution
state: Gauteng
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Barcelona
country: Spain
facility: Local Institution
city: Gijon
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Santander
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Kungalv
country: Sweden
facility: Local Institution
city: Sundsvall
country: Sweden
facility: Local Institution
city: Uppsala
country: Sweden
facility: Local Institution
city: Vaxjo
country: Sweden
facility: Local Institution
city: Cardiff
country: United Kingdom
facility: Local Institution
state: Glamorgan
city: London
country: United Kingdom
facility: Local Institution
state: Middlesex
city: Sutton
country: United Kingdom
facility: Local Institution
state: Surrey
city: Leeds
country: United Kingdom
facility: Local Institution
state: West Yorkshire
city: Essex
country: United Kingdom
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: de Liano AG, Reig O, Mellado B, Martin C, Rull EU, Maroto JP. Prognostic and predictive value of plasma testosterone levels in patients receiving first-line chemotherapy for metastatic castrate-resistant prostate cancer. Br J Cancer. 2014 Apr 29;110(9):2201-8. doi: 10.1038/bjc.2014.189. Epub 2014 Apr 10.
citation: Araujo JC, Trudel GC, Saad F, Armstrong AJ, Yu EY, Bellmunt J, Wilding G, McCaffrey J, Serrano SV, Matveev VB, Efstathiou E, Oudard S, Morris MJ, Sizer B, Goebell PJ, Heidenreich A, de Bono JS, Begbie S, Hong JH, Richardet E, Gallardo E, Paliwal P, Durham S, Cheng S, Logothetis CJ. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1307-16. doi: 10.1016/S1470-2045(13)70479-0. Epub 2013 Nov 8.