READY: Randomized Study Comparing Docetaxel Plus Dasatinib to Docetaxel Plus Placebo in Castration-resistant Prostate Cancer
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00744497
Collaborator
(none)
1,930
186
2
81
10.4
0.1
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
1930 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
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 Start Date
:
Oct 1, 2008
Actual Primary Completion Date
:
Aug 1, 2012
Actual Study Completion Date
:
Jul 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
Drug: Placebo
Drug: Docetaxel
Drug: Prednisone
|
| Active Comparator: Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
Drug: Dasatinib
Other Names:
Drug: Docetaxel
Drug: Prednisone
|
Outcome Measures
Primary Outcome Measures
- Overall Survival: Time From Randomization to Date of Death [From randomization to death or date of last contact (maximum reached: 45 months)]
Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive.
Secondary Outcome Measures
- Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST) [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)]
Objective tumor response rate=the percentage of randomized participants with a best tumor response of partial (PR) or complete response (CR), within 42 days of end of dosing, divided by total number of patients who were evaluable (with at least 1 target lesion at baseline). By RECIST: CR=disappearance of clinical and radiologic evidence of target and nontarget lesions confirmed by another evaluation at least 6 weeks later. PR=a >30% or greater decrease in the sum of longest diameter (LD) of target lesions in reference to the baseline sum LD confirmed by another evaluation at least 6 weeks later. Stable disease=neither sufficient increase to qualify for PD nor shrinkage to qualify for PR, and at least 8 weeks since start of study therapy. Progressive disease=a 20% or greater increase in sum of LD of all target lesions, taking as reference the smallest sum of LD at or following baseline, or unequivocal progression on existing nontarget lesions, or new lesions are present.
- Time to First Skeletal-related Event (SRE) [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)]
Time to first SRE is defined as the time in months from the date of randomization to the date of first SRE (unless SRE occurred while the patient was undergoing subsequent cancer therapy). Participants with a first SRE while on subsequent cancer therapy, those who died without a reported SRE, and those who did not have an SRE were censored on the date of their last SRE assessment prior to start of subsequent cancer therapy, if any. Participants who had no SRE assessments were censored on the day they were randomized.
- Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline [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)]
The percentage of participants who had an on-study uNTx value confirmed (at least 3 weeks later) within normal limits (or ≥3 and <60 nmol/mmol creatinine, if normal limits were missing) or an on-study uNTx level reduction from baseline of ≥35%, even when on-study uNTx value remained abnormal.
- Progression-free Survival (PFS) [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)]
PFS is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Those who progressed or died while on subsequent cancer therapy and those who did not die or progress were censored at their last radiologic bone scan/imaging, skeletal related-event, or tumor assessment or at measurement of prostate specific antigen levels, whichever occurred last prior to start of subsequent cancer therapy ,if any. Participants with no assessments were censored on the day of randomization.
- Time to Prostate Specific Antigen (PSA) Progression [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)]
PSA progression is defined as the time from randomization to the date of the first PSA level measurement that led to confirmed PSA progression, for participants who had not started subsequent cancer therapy. For participants who did not progress or who progressed on cancer therapy, PSA progression is defined as the time from randomization to the date of the last PSA level measurement before the start of cancer therapy, if any. Participants who had no on-study PSA level measurements were censored on the day they were randomized.
- Percentage of Participants With a Reduction in Pain Intensity From Baseline [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)]
The percentage of participants with a reduction in pain intensity from baseline was defined as the number of participants who achieved a 30% or more decrease in pain intensity from baseline for at least 2 consecutive pain assessments (at least 14 days apart) within 14 days of end of dosing divided by the number of randomized participants who had a baseline pain intensity of at least 2. Pain intensity was assessed based on question 3 of the brief pain inventory questionnaire.
Other Outcome Measures
- Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths [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]
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug
- Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest [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]
AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. AEs of Special Interest=recognized events in other agents within this drug class or events for which safety data from nonclinical and clinical studies with dasatinib indicate that careful evaluation is warranted. Drug-related=having certain, probable, possible, or missing relationship to study drug. Drug-related AEs of Special Interest are identified by the medical and safety representatives of the sponsor based on MedDRA preferred terms or laboratory data. ANC=absolute neutrophil count.
- Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology [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.]
Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening ). Grade 3 and 4 criteria are defined as follows: Absolute neutrophil count, Grade 3, neutrophils <1.0-0.5*10^9/L; Grade 4, <0.5*10^9/L. Hemoglobin, Grade 3, <4.9-4.0 mmol/L; Grade 4, <4.0 mmol/L. Platelets, Grade 3, <50.0-25.0*10^9/L; Grade 4, <25.0*10^9/L. Leukocytes, Grade 3, <2.0-1.0*10^9/L; Grade 4, <1.0*10^9/L.
- Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes [At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.]
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening). ALP, ALT, and AST, Grade 3, >5.0-20.0*ULN; Grade 4, >20.0*ULN. Total bilirubin, Grade 3, >3.0-10.0*ULN; Grade 4, >10.0*ULN. Creatinine, Grade 3, >3.0-6.0*ULN; Grade 4, >6.0*ULN. Hypercalcemia(serum calcium, mmol/L), Grade 3, >3.1-3.4; Grade 4, >3.4. Hypocalcemia (serum calcium, mmol/L), Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia(serum calcium, mmol/L), Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia(serum calcium, mmol/L), Grade 3, <3.0-2.5; Grade 4, <2.5. Hypernatremia (serum calcium, mmol/L), Grade 3, >155-160; Grade 4, >160. Hyponatremia (serum sodium, mmol/L), Grade 3, <130-120; Grade 4, <120. Phosphorus (serum sodium, mmol/L), Grade 3, <0.6-0.3; Grade 4, <0.3.
- Number of Participants With Abnormal Results in Urinalysis [At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.]
Abnormal=positive, defined as the presence of >=30 mg/dL of protein; a small, moderate, or large amount of blood; or >0 g/dL glucose in urine. BL=baseline; neg=negative
- Number of Participants by Maximal On-study Fridericia-corrected QTc Interval [At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing]
QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included.
- Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval [At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing]
QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included.
- 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 [At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated]
BL=baseline; OS=on-study
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
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/mm3; absolute neutrophil count >=1,500/mm3; platelet count >=100,000/mm^3; creatinine level <=1.5upper limit of normal (ULN); bilirubin <=ULN; aspartate aminotransferase <=2.5ULN; 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of South Alabama / Mitchell Cancer Institute | Mobile | Alabama | United States | 36604 |
| 2 | Southern Cancer Center | Mobile | Alabama | United States | 36608 |
| 3 | Alaska Clinical Research Center, Llc | Anchorage | Alaska | United States | 99508 |
| 4 | Highlands Oncology Group | Fayetteville | Arkansas | United States | 72703 |
| 5 | Compassionate Cancer Care Medical Group, Inc. | Corona | California | United States | 92879 |
| 6 | Desert Hematology Oncology Medical Group | Rancho Mirage | California | United States | 92270 |
| 7 | Compassionate Cancer Care Medical Group Inc | Riverside | California | United States | 92501 |
| 8 | Sharp Clinical Oncology Research | San Diego | California | United States | 92123 |
| 9 | Va San Diego Healthcare System | San Diego | California | United States | 92161 |
| 10 | Edward Alexson, Md, Inc. | Santa Ana | California | United States | 92705 |
| 11 | Connecticut Oncology Group | Middletown | Connecticut | United States | 06457 |
| 12 | Va Connecticut Healthcare System | West Haven | Connecticut | United States | 06516 |
| 13 | Gwinnett Hospital System Inc. | Lawrenceville | Georgia | United States | 30046 |
| 14 | University Of Chicago | Chicago | Illinois | United States | 60637 |
| 15 | Midwestern Regional Medical Center | Zion | Illinois | United States | 60099 |
| 16 | Fort Wayne Medical Oncology And Hematology Inc | Fort Wayne | Indiana | United States | 46845 |
| 17 | Cancer Center Of Kansas | Wichita | Kansas | United States | 67214 |
| 18 | Maine Center For Cancer Medicine | Scarborough | Maine | United States | 04074 |
| 19 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 20 | Jackson Oncology Associates, Pllc | Jackson | Mississippi | United States | 39202 |
| 21 | North Mississippi Hematology And Oncology Associates, Ltd | Tupelo | Mississippi | United States | 38801 |
| 22 | New York Oncology Hematology, Pc | Albany | New York | United States | 12206 |
| 23 | New York Oncology Hematology, Pc | Albany | New York | United States | 12208 |
| 24 | Samuel S. Stratton Vamc | Albany | New York | United States | 12208 |
| 25 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 26 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 27 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 28 | Piedmont Hematology Oncology Associates, Pllc | Winston-salem | North Carolina | United States | 27103 |
| 29 | Summa Health System | Akron | Ohio | United States | 44304 |
| 30 | Mid Ohio Oncology/Hematology, Inc,Dba | Columbus | Ohio | United States | 43219 |
| 31 | Providence Portland Med Ctr | Portland | Oregon | United States | 97213 |
| 32 | Regional Hemetology Oncology, Pc | Langhorne | Pennsylvania | United States | 19047 |
| 33 | Upmc Cancer Pavilion | Pittsburgh | Pennsylvania | United States | 15232 |
| 34 | Va Pittsburgh Healthcare System | Pittsburgh | Pennsylvania | United States | 15240 |
| 35 | Associates In Hematology & Oncology, P.C. | Upland | Pennsylvania | United States | 19013 |
| 36 | The Miriam Hospital | Providence | Rhode Island | United States | 02906 |
| 37 | Cancer Centers Of The Carolinas | Greenville | South Carolina | United States | 29615 |
| 38 | Boston Baskin Cancer Foundation | Memphis | Tennessee | United States | 38120 |
| 39 | Cancer Specialists Of South Texas, Pa | Corpus Christi | Texas | United States | 78412 |
| 40 | The University Of Texas Md Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 41 | Providence Regional Cancer System | Lacey | Washington | United States | 98503 |
| 42 | University Of Washington | Seattle | Washington | United States | 98109 |
| 43 | Dean Hematology And Oncology Clinic | Madison | Wisconsin | United States | 53717 |
| 44 | Local Institution | Caba | Buenos Aires | Argentina | 1417 |
| 45 | Local Institution | Capital Federal | Buenos Aires | Argentina | 1425 |
| 46 | Local Institution | Capital Federal | Buenos Aires | Argentina | 1426 |
| 47 | Local Institution | Capital Federal | Buenos Aires | Argentina | C1405BCJ |
| 48 | Local Institution | La Plata | Buenos Aires | Argentina | 1900 |
| 49 | Local Institution | Ramos Mejia | Buenos Aires | Argentina | 1234 |
| 50 | Local Institution | Cipolletti | Rio Negro | Argentina | R8324BEH |
| 51 | Local Institution | Rosario | Santa Fe | Argentina | S2000CVD |
| 52 | Local Institution | Rosario | Santa Fe | Argentina | S2000DSK |
| 53 | Local Institution | San Miguel De Tucuman | Tucuman | Argentina | T4000IAK |
| 54 | Local Institution | Buenos Aires | Argentina | C1181ACH | |
| 55 | Local Institution | Buenos Aires | Argentina | C1280AEB | |
| 56 | Local Institution | Buenos Aires | Argentina | C1426ANZ | |
| 57 | Local Institution | Cordaba | Argentina | 5000 | |
| 58 | Local Institution | Coffs Harbour | New South Wales | Australia | 2450 |
| 59 | Local Institution | Lismore | New South Wales | Australia | 2480 |
| 60 | Local Institution | Port Macquarie | New South Wales | Australia | 2444 |
| 61 | Local Institution | Sydney | New South Wales | Australia | 2076 |
| 62 | Local Institution | Douglas | Queensland | Australia | 4814 |
| 63 | Local Institution | Milton | Queensland | Australia | 4164 |
| 64 | Local Institution | Kurralta Park | South Australia | Australia | 5037 |
| 65 | Local Institution | Hobart | Tasmania | Australia | 7000 |
| 66 | Local Institution | Frankston | Victoria | Australia | 3199 |
| 67 | Local Institution | Ringwood | Victoria | Australia | 3135 |
| 68 | Local Institution | Fremantle | Western Australia | Australia | 6162 |
| 69 | Local Institution | Salvador | Bahia | Brazil | 41950 |
| 70 | Local Institution | Porto Alegre | Rio Grande Do Sul | Brazil | 90610 |
| 71 | Local Institution | Barretos | Sao Paulo | Brazil | 14784 |
| 72 | Local Institution | Campinas | Sao Paulo | Brazil | 13083 |
| 73 | Local Institution | Jau | Sao Paulo | Brazil | 17210 |
| 74 | Local Institution | Santo Andre | Sao Paulo | Brazil | 09060 |
| 75 | Local Institution | Rio De Janeiro | Brazil | 20230 | |
| 76 | Local Institution | Rio De Janeiro | Brazil | 22551 | |
| 77 | Local Institution | Edmonton | Alberta | Canada | T6G 1Z2 |
| 78 | Local Institution | Abbottsford | British Columbia | Canada | V2S 3N5 |
| 79 | Local Institution | Moncton | New Brunswick | Canada | E1C 6Z8 |
| 80 | Local Institution | Ottawa | Ontario | Canada | K1H 8L6 |
| 81 | Local Institution | Owen Sound | Ontario | Canada | N4K 2J1 |
| 82 | Local Institution | Sudbury | Ontario | Canada | P3E 5J1 |
| 83 | Local Institution | Thunder Bay | Ontario | Canada | P7B 6V4 |
| 84 | Local Institution | Greenfield Park | Quebec | Canada | J4V 2H1 |
| 85 | Local Institution | Montreal | Quebec | Canada | H2W 1S6 |
| 86 | Local Institution | Montreal | Quebec | Canada | H2W 1Y5 |
| 87 | Local Institution | Rimouski | Quebec | Canada | G5L 5T1 |
| 88 | Local Institution | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 89 | Local Institution | Regina | Saskatchewan | Canada | S4T 7T1 |
| 90 | Local Institution | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 91 | Local Institution | Brno | Czech Republic | 656 53 | |
| 92 | Local Institution | Hradec Kralove | Czech Republic | 500 05 | |
| 93 | Local Institution | Praha 2 | Czech Republic | 128 08 | |
| 94 | Local Institution | Praha 8 | Czech Republic | 180 81 | |
| 95 | Local Institution | Turku | Finland | 20520 | |
| 96 | Local Institution | Vaasa | Finland | 65130 | |
| 97 | Local Institution | Avignon | France | 84082 | |
| 98 | Local Institution | Besancon Cedex | France | 25030 | |
| 99 | Local Institution | Caen | France | 14076 | |
| 100 | Local Institution | Creteil | France | 94010 | |
| 101 | Local Institution | Paris | France | 75908 | |
| 102 | Local Institution | St Genis Laval | France | 69230 | |
| 103 | Local Institution | Strasbourg | France | 67085 | |
| 104 | Local Institution | Aachen | Germany | 52074 | |
| 105 | Local Institution | Berlin | Germany | 12200 | |
| 106 | Local Institution | Erlangen | Germany | 91054 | |
| 107 | Local Institution | Essen | Germany | 45122 | |
| 108 | Local Institution | Kirchheim | Germany | 73230 | |
| 109 | Local Institution | Markkleeberg | Germany | 04416 | |
| 110 | Local Institution | Athens | Greece | 11528 | |
| 111 | Local Institution | Budapest | Hungary | 1122 | |
| 112 | Local Institution | Kecskemet | Hungary | 6000 | |
| 113 | Local Institution | Zalaegerszeg | Hungary | 8900 | |
| 114 | Local Institution | Trivandrum | Kerala | India | 695011 |
| 115 | Local Institution | Mumbai | Maharashtra | India | 400026 |
| 116 | Local Institution | Pune | Maharashtra | India | 411001 |
| 117 | Local Institution | Pune | Maharashtra | India | 411004 |
| 118 | Local Institution | Ahmedabad | India | 380009 | |
| 119 | Local Institution | Jaipur | India | 302013 | |
| 120 | Local Institution | Kolkata | India | 700 053 | |
| 121 | Local Institution | Kolkatta | India | 700 016 | |
| 122 | Local Institution | Dublin 7 | Dublin | Ireland | |
| 123 | Local Institution | Tallaght | Dublin | Ireland | DUBLIN 24 |
| 124 | Local Institution | Cork | Ireland | ||
| 125 | Local Institution | Dublin | Ireland | 7 | |
| 126 | Local Institution | Arezzo | Italy | 52100 | |
| 127 | Local Institution | Genova | Italy | 16132 | |
| 128 | Local Institution | Lecce | Italy | 73100 | |
| 129 | Local Institution | Milan | Italy | 20141 | |
| 130 | Local Institution | Napoli | Italy | 80131 | |
| 131 | Local Institution | Perugia | Italy | 06132 | |
| 132 | Local Institution | Roma | Italy | 00161 | |
| 133 | Local Institution | Seoul | Korea, Republic of | 120-752 | |
| 134 | Local Institution | Seoul | Korea, Republic of | 135-710 | |
| 135 | Local Institution | Seoul | Korea, Republic of | 135-720 | |
| 136 | Local Institution | Seoul | Korea, Republic of | 138-736 | |
| 137 | Local Institution | Tijuana | Baja California | Mexico | 22010 |
| 138 | Local Institution | Df | Distrito Federal | Mexico | 06720 |
| 139 | Local Institution | Mexico D.f. | Distrito Federal | Mexico | 14050 |
| 140 | Local Institution | Tlalpan | Distrito Federal | Mexico | 14000 |
| 141 | Local Institution | Tlalpan | Distrito Federal | Mexico | 14080 |
| 142 | Local Institution | Huixquilucan | Estado De Mexico | Mexico | 52763 |
| 143 | Local Institution | Toluca | Estado De Mexico | Mexico | 50180 |
| 144 | Local Institution | Guadalajara | Jalisco | Mexico | 44280 |
| 145 | Local Institution | Zapopan | Jalisco | Mexico | 45150 |
| 146 | Local Institution | Monterrey | Nuevo Leon | Mexico | 64460 |
| 147 | Local Institution | Mexico | Queretaro | Mexico | 76200 |
| 148 | Local Institution | Stavanger | Norway | 4068 | |
| 149 | Local Institution | Callao | Peru | CALLAO 2 | |
| 150 | Local Institution | Lima | Peru | 11 | |
| 151 | Local Institution | Lima | Peru | 34 | |
| 152 | Local Institution | Lima | Peru | 41 | |
| 153 | Local Institution | Lima | Peru | LIMA 11 | |
| 154 | Local Institution | Lima | Peru | LIMA 29 | |
| 155 | Local Institution | Bialystok | Poland | 15-027 | |
| 156 | Local Institution | Lodz | Poland | 93-509 | |
| 157 | Local Institution | Warszawa | Poland | 02-781 | |
| 158 | Local Institution | Baia Mare | Romania | 430031 | |
| 159 | Local Institution | Cluj Napoca | Romania | 400015 | |
| 160 | Local Institution | Timisoara, Timis | Romania | 300239 | |
| 161 | Local Institution | Moscow | Russian Federation | 115478 | |
| 162 | Local Institution | Moscow | Russian Federation | 117997 | |
| 163 | Local Institution | St Petersburg | Russian Federation | 197022 | |
| 164 | Local Institution | St Petersburg | Russian Federation | 197758 | |
| 165 | Local Institution | Bloemfontein | Free State | South Africa | 9301 |
| 166 | Local Institution | Pretoria | Gauteng | South Africa | 0181 |
| 167 | Local Institution | Saxonwold | Gauteng | South Africa | 2199 |
| 168 | Local Institution | Barcelona | Spain | 08003 | |
| 169 | Local Institution | Barcelona | Spain | 08025 | |
| 170 | Local Institution | Barcelona | Spain | 08208 | |
| 171 | Local Institution | Gijon | Spain | 33394 | |
| 172 | Local Institution | Madrid | Spain | 28007 | |
| 173 | Local Institution | Madrid | Spain | 28033 | |
| 174 | Local Institution | Madrid | Spain | 28050 | |
| 175 | Local Institution | Santander | Spain | 39008 | |
| 176 | Local Institution | Sevilla | Spain | 41013 | |
| 177 | Local Institution | Valencia | Spain | 46009 | |
| 178 | Local Institution | Kungalv | Sweden | 442 83 | |
| 179 | Local Institution | Sundsvall | Sweden | 851 86 | |
| 180 | Local Institution | Uppsala | Sweden | 751 85 | |
| 181 | Local Institution | Vaxjo | Sweden | 351 85 | |
| 182 | Local Institution | Cardiff | Glamorgan | United Kingdom | CF14 2TL |
| 183 | Local Institution | London | Middlesex | United Kingdom | W12 0NN |
| 184 | Local Institution | Sutton | Surrey | United Kingdom | SM2 5PT |
| 185 | Local Institution | Leeds | West Yorkshire | United Kingdom | LS8 7TF |
| 186 | Local Institution | Essex | United Kingdom | CO3 3NB |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00744497
Other Study ID Numbers:
- CA180-227
- 2008-000701-11
First Posted:
Sep 1, 2008
Last Update Posted:
Oct 17, 2016
Last Verified:
Aug 1, 2016
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 1930 participants enrolled, 1522 randomized to a treatment group (762 dasatinib, 760 placebo). 408 not randomized. Reasons for non-randomization include 7 adverse events, 42 withdrew consent, 6 deaths, 2 lost to follow up, 3 poor/non compliance, 332 no longer met study criteria, 1 administrative reason by sponsor, and 15 non-specified reasons. |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Period Title: Overall Study | ||
| STARTED | 760 | 762 |
| Received Treatment | 757 | 761 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 760 | 762 |
Baseline Characteristics
| Arm/Group Title | Placebo | Dasatinib | Total |
|---|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Total of all reporting groups |
| Overall Participants | 760 | 762 | 1522 |
| Age, Customized (participants) [Number] | |||
| Younger than 65 years |
263
34.6%
|
251
32.9%
|
514
33.8%
|
| 65 to younger than 75 years |
323
42.5%
|
333
43.7%
|
656
43.1%
|
| 75 years or older |
174
22.9%
|
178
23.4%
|
352
23.1%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
0
0%
|
0
0%
|
0
0%
|
| Male |
760
100%
|
762
100%
|
1522
100%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| Asian |
56
7.4%
|
55
7.2%
|
111
7.3%
|
| Native Hawaiian or Other Pacific Islander |
1
0.1%
|
1
0.1%
|
2
0.1%
|
| Black or African American |
34
4.5%
|
23
3%
|
57
3.7%
|
| White |
645
84.9%
|
656
86.1%
|
1301
85.5%
|
| Other |
24
3.2%
|
27
3.5%
|
51
3.4%
|
| Type of metastatic disease (Number) [Number] | |||
| Bone disease only |
286
37.6%
|
307
40.3%
|
593
39%
|
| Visceral/nodal disease only |
73
9.6%
|
80
10.5%
|
153
10.1%
|
| Both bone and visceral/nodal disease |
399
52.5%
|
373
49%
|
772
50.7%
|
| No evidence of metastatic disease |
2
0.3%
|
2
0.3%
|
4
0.3%
|
Outcome Measures
| Title | Overall Survival: Time From Randomization to Date of Death |
|---|---|
| Description | Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive. |
| Time Frame | From randomization to death or date of last contact (maximum reached: 45 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were randomized to receive any treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 760 | 762 |
| Median (95% Confidence Interval) [Months] |
21.2
|
21.5
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Confidence intervals for median overall survival calculated using Brookmeyer and Crowley method. Compared survival in arms by 2-sided, alpha=0.0447 level, log-rank test, stratified by bisphosphonate intake (yes/no) and urinary N-telopeptide category (<60 vs ≥60 nmol/mmol creatinine) defined at randomization. Null hypothesis was survival equal in both arms. Power calculations were that ≥858 deaths would lead to ≥90% power at 5% level for rejecting null hypothesis, given true hazard ratio of 0.8. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.9009 |
| Comments | An interim analysis on survival was performed and the final test was corrected for multiplicity. | |
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.99 | |
| Confidence Interval |
(2-Sided) 95.53% 0.87 to 1.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST) |
|---|---|
| Description | Objective tumor response rate=the percentage of randomized participants with a best tumor response of partial (PR) or complete response (CR), within 42 days of end of dosing, divided by total number of patients who were evaluable (with at least 1 target lesion at baseline). By RECIST: CR=disappearance of clinical and radiologic evidence of target and nontarget lesions confirmed by another evaluation at least 6 weeks later. PR=a >30% or greater decrease in the sum of longest diameter (LD) of target lesions in reference to the baseline sum LD confirmed by another evaluation at least 6 weeks later. Stable disease=neither sufficient increase to qualify for PD nor shrinkage to qualify for PR, and at least 8 weeks since start of study therapy. Progressive disease=a 20% or greater increase in sum of LD of all target lesions, taking as reference the smallest sum of LD at or following baseline, or unequivocal progression on existing nontarget lesions, or new lesions are present. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with at least 1 target lesion at baseline |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 383 | 381 |
| Number (95% Confidence Interval) [Percentage of participants] |
31.85
4.2%
|
30.45
4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.935 | |
| Confidence Interval |
(2-Sided) 95% 0.688 to 1.271 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to First Skeletal-related Event (SRE) |
|---|---|
| Description | Time to first SRE is defined as the time in months from the date of randomization to the date of first SRE (unless SRE occurred while the patient was undergoing subsequent cancer therapy). Participants with a first SRE while on subsequent cancer therapy, those who died without a reported SRE, and those who did not have an SRE were censored on the date of their last SRE assessment prior to start of subsequent cancer therapy, if any. Participants who had no SRE assessments were censored on the day they were randomized. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were randomized to receive any treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 760 | 762 |
| Median (95% Confidence Interval) [Months] |
31.1
|
NA
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.81 | |
| Confidence Interval |
(2-Sided) 95% 0.64 to 1.02 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline |
|---|---|
| Description | The percentage of participants who had an on-study uNTx value confirmed (at least 3 weeks later) within normal limits (or ≥3 and <60 nmol/mmol creatinine, if normal limits were missing) or an on-study uNTx level reduction from baseline of ≥35%, even when on-study uNTx value remained abnormal. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who entered the study with baseline urinary N-telopeptide values higher than the upper limit of normal (ULN), or ≥60 nmol/mmol creatinine, if ULN was missing |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 335 | 321 |
| Number (95% Confidence Interval) [Percentage of participants] |
60.60
8%
|
66.04
8.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 1.280 | |
| Confidence Interval |
(2-Sided) 95% 0.930 to 1.763 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Progression-free Survival (PFS) |
|---|---|
| Description | PFS is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Those who progressed or died while on subsequent cancer therapy and those who did not die or progress were censored at their last radiologic bone scan/imaging, skeletal related-event, or tumor assessment or at measurement of prostate specific antigen levels, whichever occurred last prior to start of subsequent cancer therapy ,if any. Participants with no assessments were censored on the day of randomization. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were randomized to receive any treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 760 | 762 |
| Median (95% Confidence Interval) [Months] |
11.1
|
11.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.92 | |
| Confidence Interval |
(2-Sided) 95% 0.82 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Time to Prostate Specific Antigen (PSA) Progression |
|---|---|
| Description | PSA progression is defined as the time from randomization to the date of the first PSA level measurement that led to confirmed PSA progression, for participants who had not started subsequent cancer therapy. For participants who did not progress or who progressed on cancer therapy, PSA progression is defined as the time from randomization to the date of the last PSA level measurement before the start of cancer therapy, if any. Participants who had no on-study PSA level measurements were censored on the day they were randomized. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were randomized to receive any treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 760 | 762 |
| Median (95% Confidence Interval) [Months] |
6.9
|
7.2
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The hazard ratio is presented for experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.89 | |
| Confidence Interval |
(2-Sided) 95% 0.79 to 1.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Percentage of Participants With a Reduction in Pain Intensity From Baseline |
|---|---|
| Description | The percentage of participants with a reduction in pain intensity from baseline was defined as the number of participants who achieved a 30% or more decrease in pain intensity from baseline for at least 2 consecutive pain assessments (at least 14 days apart) within 14 days of end of dosing divided by the number of randomized participants who had a baseline pain intensity of at least 2. Pain intensity was assessed based on question 3 of the brief pain inventory questionnaire. |
| Time Frame | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants with a baseline pain intensity of 2 or greater |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 467 | 419 |
| Number (95% Confidence Interval) [Percentage of participants] |
71.52
9.4%
|
66.59
8.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Dasatinib |
|---|---|---|
| Comments | Since superiority of the dasatinib treatment group was not demonstrated for Overall Survival, secondary endpoints were not tested. The odds ratio is presented for of experimental to control group. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Odds Ratio (OR) |
| Estimated Value | 0.791 | |
| Confidence Interval |
(2-Sided) 95% 0.594 to 1.052 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths |
|---|---|
| Description | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Drug-related=having certain, probable, possible, or missing relationship to study drug |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| All deaths |
505
66.4%
|
506
66.4%
|
| Deaths within 30 days of end of treatment |
50
6.6%
|
79
10.4%
|
| All SAEs |
317
41.7%
|
381
50%
|
| Drug-related SAEs |
90
11.8%
|
150
19.7%
|
| All Drug-related AEs |
482
63.4%
|
553
72.6%
|
| Drug-related AEs leading to discontinuation |
76
10%
|
144
18.9%
|
| Title | Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest |
|---|---|
| Description | AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. AEs of Special Interest=recognized events in other agents within this drug class or events for which safety data from nonclinical and clinical studies with dasatinib indicate that careful evaluation is warranted. Drug-related=having certain, probable, possible, or missing relationship to study drug. Drug-related AEs of Special Interest are identified by the medical and safety representatives of the sponsor based on MedDRA preferred terms or laboratory data. ANC=absolute neutrophil count. |
| Time Frame | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| Diarrhea |
167
22%
|
229
30.1%
|
| Nausea/vomiting |
127
16.7%
|
170
22.3%
|
| Fatigue |
216
28.4%
|
236
31%
|
| Myalgias/arthralgias |
29
3.8%
|
29
3.8%
|
| Rash |
46
6.1%
|
72
9.4%
|
| Gastrointestinal tract bleeding |
6
0.8%
|
14
1.8%
|
| Central nervous system bleeding |
1
0.1%
|
2
0.3%
|
| Other hemorrhage |
14
1.8%
|
24
3.1%
|
| Pulmonary arterial hypertension |
0
0%
|
0
0%
|
| Fluid retention: Superficial edema |
77
10.1%
|
76
10%
|
| Fluid retention: Pleural effusion |
13
1.7%
|
87
11.4%
|
| Fluid retention: Other |
37
4.9%
|
52
6.8%
|
| Title | Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology |
|---|---|
| Description | Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening ). Grade 3 and 4 criteria are defined as follows: Absolute neutrophil count, Grade 3, neutrophils <1.0-0.5*10^9/L; Grade 4, <0.5*10^9/L. Hemoglobin, Grade 3, <4.9-4.0 mmol/L; Grade 4, <4.0 mmol/L. Platelets, Grade 3, <50.0-25.0*10^9/L; Grade 4, <25.0*10^9/L. Leukocytes, Grade 3, <2.0-1.0*10^9/L; Grade 4, <1.0*10^9/L. |
| Time Frame | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| Absolute neutrophil count (All grades) |
84
11.1%
|
161
21.1%
|
| Absolute neutrophil count (Grades 3 and 4) |
41
5.4%
|
46
6%
|
| Hemoglobin (All grades) |
712
93.7%
|
720
94.5%
|
| Hemoglobin (Grades 3 and 4) |
44
5.8%
|
59
7.7%
|
| Platelets (All grades) |
108
14.2%
|
100
13.1%
|
| Platelets (Grades 3 and 4) |
6
0.8%
|
3
0.4%
|
| Leukocytes (All grades) |
128
16.8%
|
149
19.6%
|
| Leukocytes (Grades 3 and 4) |
32
4.2%
|
30
3.9%
|
| Title | Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes |
|---|---|
| Description | ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening). ALP, ALT, and AST, Grade 3, >5.0-20.0*ULN; Grade 4, >20.0*ULN. Total bilirubin, Grade 3, >3.0-10.0*ULN; Grade 4, >10.0*ULN. Creatinine, Grade 3, >3.0-6.0*ULN; Grade 4, >6.0*ULN. Hypercalcemia(serum calcium, mmol/L), Grade 3, >3.1-3.4; Grade 4, >3.4. Hypocalcemia (serum calcium, mmol/L), Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia(serum calcium, mmol/L), Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia(serum calcium, mmol/L), Grade 3, <3.0-2.5; Grade 4, <2.5. Hypernatremia (serum calcium, mmol/L), Grade 3, >155-160; Grade 4, >160. Hyponatremia (serum sodium, mmol/L), Grade 3, <130-120; Grade 4, <120. Phosphorus (serum sodium, mmol/L), Grade 3, <0.6-0.3; Grade 4, <0.3. |
| Time Frame | At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| ALP (All grades) |
447
58.8%
|
375
49.2%
|
| ALP (Grades 3 and 4) |
91
12%
|
68
8.9%
|
| ALT (All grades) |
186
24.5%
|
256
33.6%
|
| ALT (Grades 3 and 4) |
5
0.7%
|
6
0.8%
|
| AST (All grades) |
212
27.9%
|
266
34.9%
|
| AST (Grades 3 and 4) |
4
0.5%
|
5
0.7%
|
| Total bilirubin (All grades) |
49
6.4%
|
41
5.4%
|
| Total bilirubin (Grades 3 and 4) |
1
0.1%
|
3
0.4%
|
| Creatinine (All grades) |
153
20.1%
|
184
24.1%
|
| Creatinine (Grades 3 and 4) |
3
0.4%
|
5
0.7%
|
| Hypercalcemia (All grades) |
56
7.4%
|
34
4.5%
|
| Hypercalcemia (Grades 3 and 4) |
1
0.1%
|
1
0.1%
|
| Hypocalcemia (All grades) |
308
40.5%
|
377
49.5%
|
| Hypocalcemia (Grades 3 and 4) |
23
3%
|
25
3.3%
|
| Hyperkalemia (All grades) |
164
21.6%
|
152
19.9%
|
| Hyperkalemia (Grades 3 and 4) |
11
1.4%
|
14
1.8%
|
| Hypokalemia (All grades) |
107
14.1%
|
152
19.9%
|
| Hypokalemia (Grades 3 and 4) |
6
0.8%
|
16
2.1%
|
| Hypernatremia (All grades) |
93
12.2%
|
101
13.3%
|
| Hypernatremia (Grades 3 and 4) |
0
0%
|
0
0%
|
| Hyponatremia (All grades) |
230
30.3%
|
241
31.6%
|
| Hyponatremia (Grades 3 and 4) |
36
4.7%
|
43
5.6%
|
| Phosporus (All grades) |
189
24.9%
|
257
33.7%
|
| Phosphorus (Grades 3 and 4) |
43
5.7%
|
93
12.2%
|
| Title | Number of Participants With Abnormal Results in Urinalysis |
|---|---|
| Description | Abnormal=positive, defined as the presence of >=30 mg/dL of protein; a small, moderate, or large amount of blood; or >0 g/dL glucose in urine. BL=baseline; neg=negative |
| Time Frame | At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment. |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| Protein, urine: postive |
246
32.4%
|
336
44.1%
|
| Blood, urine: positive |
289
38%
|
307
40.3%
|
| Glucose, urine: positive |
179
23.6%
|
154
20.2%
|
| Title | Number of Participants by Maximal On-study Fridericia-corrected QTc Interval |
|---|---|
| Description | QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included. |
| Time Frame | At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment. n=number evaluable |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| <450 msecs (n=600, 548) |
550
72.4%
|
497
65.2%
|
| 450-500 msecs (n=600, 548) |
43
5.7%
|
48
6.3%
|
| >500 msecs (n=600, 548) |
7
0.9%
|
3
0.4%
|
| Title | Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval |
|---|---|
| Description | QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included. |
| Time Frame | At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received treatment. n=number evaluable |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 757 | 761 |
| 0 to 30 msecs increase (n=591, 540) |
203
26.7%
|
199
26.1%
|
| >30 to 60 msecs increase (n=591, 540) |
52
6.8%
|
47
6.2%
|
| >60 msecs increase (n=591, 540) |
32
4.2%
|
26
3.4%
|
| Decrease (n=591, 540) |
304
40%
|
268
35.2%
|
| Title | 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 |
|---|---|
| Description | BL=baseline; OS=on-study |
| Time Frame | At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who were randomized to receive any treatment |
| Arm/Group Title | Placebo | Dasatinib |
|---|---|---|
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily |
| Measure Participants | 760 | 762 |
| Pericardial effusion at BL/absent OS |
3
0.4%
|
1
0.1%
|
| Pericardial effusion at BL/present OS |
0
0%
|
1
0.1%
|
| Pericardial effusion at BL/not reported OS |
1
0.1%
|
0
0%
|
| Pericardial effusion absent at BL/ absent OS |
584
76.8%
|
545
71.5%
|
| Pericardial effusion absent at BL/present OS |
24
3.2%
|
26
3.4%
|
| Pericardial effusion absent at BL/not reported OS |
132
17.4%
|
184
24.1%
|
| Pericardial not reported at BL |
16
2.1%
|
5
0.7%
|
| LVEF OS <40% |
2
0.3%
|
2
0.3%
|
| LVEF OS >=40% |
607
79.9%
|
566
74.3%
|
| LVEF not reported OS |
151
19.9%
|
194
25.5%
|
Adverse Events
| Time Frame | Day 1 up to 30 days post last dose of study therapy | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Study initiated: October 2008; Study Completion: July 2015 | |||
| Arm/Group Title | Placebo | Dasatinib | ||
| Arm/Group Description | Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily | ||
All Cause Mortality |
||||
| Placebo | Dasatinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Placebo | Dasatinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 317/757 (41.9%) | 381/761 (50.1%) | ||
| Blood and lymphatic system disorders | ||||
| Febrile bone marrow aplasia | 0/757 (0%) | 1/761 (0.1%) | ||
| Hypochromic anaemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Leukopenia | 7/757 (0.9%) | 9/761 (1.2%) | ||
| Anaemia | 15/757 (2%) | 21/761 (2.8%) | ||
| Agranulocytosis | 1/757 (0.1%) | 0/761 (0%) | ||
| Neutropenia | 18/757 (2.4%) | 19/761 (2.5%) | ||
| Normochromic normocytic anaemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Disseminated intravascular coagulation | 0/757 (0%) | 1/761 (0.1%) | ||
| Thrombocytopenia | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Febrile neutropenia | 27/757 (3.6%) | 32/761 (4.2%) | ||
| Haemorrhagic anaemia | 0/757 (0%) | 1/761 (0.1%) | ||
| Cardiac disorders | ||||
| Supraventricular tachycardia | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Cardiopulmonary failure | 0/757 (0%) | 1/761 (0.1%) | ||
| Sinus node dysfunction | 1/757 (0.1%) | 0/761 (0%) | ||
| Acute coronary syndrome | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Coronary artery disease | 1/757 (0.1%) | 0/761 (0%) | ||
| Atrial flutter | 2/757 (0.3%) | 0/761 (0%) | ||
| Cardiac arrest | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Cardio-respiratory arrest | 0/757 (0%) | 1/761 (0.1%) | ||
| Tachycardia | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Acute myocardial infarction | 0/757 (0%) | 3/761 (0.4%) | ||
| Cardiac failure | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Myocardial ischaemia | 2/757 (0.3%) | 2/761 (0.3%) | ||
| Pericardial effusion | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Atrial fibrillation | 8/757 (1.1%) | 8/761 (1.1%) | ||
| Atrioventricular block second degree | 0/757 (0%) | 1/761 (0.1%) | ||
| Left ventricular dysfunction | 0/757 (0%) | 1/761 (0.1%) | ||
| Supraventricular tachyarrhythmia | 0/757 (0%) | 1/761 (0.1%) | ||
| Cardiac failure congestive | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Myocardial infarction | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Angina pectoris | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Arrhythmia | 0/757 (0%) | 2/761 (0.3%) | ||
| Cardiac disorder | 0/757 (0%) | 1/761 (0.1%) | ||
| Congenital, familial and genetic disorders | ||||
| Hydrocele | 1/757 (0.1%) | 0/761 (0%) | ||
| Eye disorders | ||||
| Maculopathy | 1/757 (0.1%) | 0/761 (0%) | ||
| Amaurosis fugax | 1/757 (0.1%) | 0/761 (0%) | ||
| Gastrointestinal disorders | ||||
| Abdominal hernia | 1/757 (0.1%) | 0/761 (0%) | ||
| Dyspepsia | 1/757 (0.1%) | 0/761 (0%) | ||
| Enterovesical fistula | 1/757 (0.1%) | 0/761 (0%) | ||
| Gastric haemorrhage | 0/757 (0%) | 1/761 (0.1%) | ||
| Large intestinal obstruction | 1/757 (0.1%) | 0/761 (0%) | ||
| Reflux gastritis | 1/757 (0.1%) | 0/761 (0%) | ||
| Stomatitis | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Colitis | 0/757 (0%) | 4/761 (0.5%) | ||
| Diverticular perforation | 1/757 (0.1%) | 0/761 (0%) | ||
| Gastritis erosive | 0/757 (0%) | 1/761 (0.1%) | ||
| Melaena | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Mouth ulceration | 0/757 (0%) | 1/761 (0.1%) | ||
| Nausea | 7/757 (0.9%) | 13/761 (1.7%) | ||
| Anal fissure | 1/757 (0.1%) | 0/761 (0%) | ||
| Anal fistula | 0/757 (0%) | 2/761 (0.3%) | ||
| Gastrooesophageal reflux disease | 1/757 (0.1%) | 0/761 (0%) | ||
| Intra-abdominal haemorrhage | 0/757 (0%) | 1/761 (0.1%) | ||
| Megacolon | 0/757 (0%) | 1/761 (0.1%) | ||
| Periodontal disease | 0/757 (0%) | 1/761 (0.1%) | ||
| Subileus | 1/757 (0.1%) | 0/761 (0%) | ||
| Duodenal ulcer haemorrhage | 0/757 (0%) | 1/761 (0.1%) | ||
| Gastric ulcer | 3/757 (0.4%) | 2/761 (0.3%) | ||
| Proctalgia | 0/757 (0%) | 1/761 (0.1%) | ||
| Proctitis | 0/757 (0%) | 1/761 (0.1%) | ||
| Volvulus | 0/757 (0%) | 1/761 (0.1%) | ||
| Abdominal pain | 3/757 (0.4%) | 6/761 (0.8%) | ||
| Abdominal pain upper | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Duodenal ulcer perforation | 1/757 (0.1%) | 0/761 (0%) | ||
| Haematochezia | 0/757 (0%) | 1/761 (0.1%) | ||
| Intestinal perforation | 0/757 (0%) | 1/761 (0.1%) | ||
| Peptic ulcer | 0/757 (0%) | 1/761 (0.1%) | ||
| Haematemesis | 2/757 (0.3%) | 0/761 (0%) | ||
| Ileus | 1/757 (0.1%) | 0/761 (0%) | ||
| Inguinal hernia | 1/757 (0.1%) | 0/761 (0%) | ||
| Rectal haemorrhage | 5/757 (0.7%) | 8/761 (1.1%) | ||
| Diarrhoea | 10/757 (1.3%) | 44/761 (5.8%) | ||
| Enteritis | 0/757 (0%) | 1/761 (0.1%) | ||
| Gastric ulcer perforation | 0/757 (0%) | 1/761 (0.1%) | ||
| Intestinal obstruction | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Vomiting | 10/757 (1.3%) | 14/761 (1.8%) | ||
| Constipation | 10/757 (1.3%) | 5/761 (0.7%) | ||
| Dysphagia | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Gastrointestinal haemorrhage | 7/757 (0.9%) | 8/761 (1.1%) | ||
| Gastrointestinal ulcer | 1/757 (0.1%) | 0/761 (0%) | ||
| Lower gastrointestinal haemorrhage | 0/757 (0%) | 2/761 (0.3%) | ||
| Oesophagitis | 1/757 (0.1%) | 0/761 (0%) | ||
| Toothache | 0/757 (0%) | 1/761 (0.1%) | ||
| Upper gastrointestinal haemorrhage | 0/757 (0%) | 3/761 (0.4%) | ||
| General disorders | ||||
| Device occlusion | 2/757 (0.3%) | 0/761 (0%) | ||
| Hyperthermia | 0/757 (0%) | 1/761 (0.1%) | ||
| Pain | 9/757 (1.2%) | 7/761 (0.9%) | ||
| Peripheral swelling | 1/757 (0.1%) | 0/761 (0%) | ||
| Pyrexia | 14/757 (1.8%) | 29/761 (3.8%) | ||
| Death | 2/757 (0.3%) | 3/761 (0.4%) | ||
| Face oedema | 0/757 (0%) | 1/761 (0.1%) | ||
| Influenza like illness | 0/757 (0%) | 1/761 (0.1%) | ||
| Mucosal inflammation | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Oedema | 0/757 (0%) | 1/761 (0.1%) | ||
| Malaise | 0/757 (0%) | 1/761 (0.1%) | ||
| Oedema peripheral | 3/757 (0.4%) | 6/761 (0.8%) | ||
| Sudden death | 3/757 (0.4%) | 0/761 (0%) | ||
| Fatigue | 9/757 (1.2%) | 15/761 (2%) | ||
| Multi-organ failure | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Performance status decreased | 0/757 (0%) | 1/761 (0.1%) | ||
| General physical health deterioration | 1/757 (0.1%) | 4/761 (0.5%) | ||
| Chest pain | 8/757 (1.1%) | 9/761 (1.2%) | ||
| Condition aggravated | 1/757 (0.1%) | 0/761 (0%) | ||
| Generalised oedema | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Disease progression | 0/757 (0%) | 2/761 (0.3%) | ||
| Localised oedema | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Asthenia | 7/757 (0.9%) | 13/761 (1.7%) | ||
| Chills | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Cholecystitis acute | 1/757 (0.1%) | 0/761 (0%) | ||
| Cholelithiasis | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Hepatic pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Hepatotoxicity | 1/757 (0.1%) | 0/761 (0%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Anaphylactic reaction | 0/757 (0%) | 1/761 (0.1%) | ||
| Drug hypersensitivity | 0/757 (0%) | 2/761 (0.3%) | ||
| Infections and infestations | ||||
| Diverticulitis | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Empyema | 1/757 (0.1%) | 0/761 (0%) | ||
| Gastroenteritis | 3/757 (0.4%) | 3/761 (0.4%) | ||
| Scrotal abscess | 1/757 (0.1%) | 0/761 (0%) | ||
| Bronchitis | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Cellulitis | 3/757 (0.4%) | 9/761 (1.2%) | ||
| Cystitis | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Oesophageal infection | 0/757 (0%) | 1/761 (0.1%) | ||
| Peritonitis | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Pyelonephritis acute | 1/757 (0.1%) | 0/761 (0%) | ||
| Tooth infection | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Cellulitis of male external genital organ | 0/757 (0%) | 1/761 (0.1%) | ||
| Lower respiratory tract infection | 0/757 (0%) | 5/761 (0.7%) | ||
| Endocarditis | 0/757 (0%) | 1/761 (0.1%) | ||
| Infection | 4/757 (0.5%) | 8/761 (1.1%) | ||
| Lobar pneumonia | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Lung infection | 0/757 (0%) | 2/761 (0.3%) | ||
| Oral candidiasis | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Respiratory tract infection | 1/757 (0.1%) | 4/761 (0.5%) | ||
| Sepsis | 6/757 (0.8%) | 7/761 (0.9%) | ||
| Upper respiratory tract infection | 0/757 (0%) | 1/761 (0.1%) | ||
| Urinary tract infection | 7/757 (0.9%) | 10/761 (1.3%) | ||
| Candida infection | 0/757 (0%) | 1/761 (0.1%) | ||
| Clostridium difficile colitis | 0/757 (0%) | 1/761 (0.1%) | ||
| Gangrene | 0/757 (0%) | 1/761 (0.1%) | ||
| Herpes zoster | 2/757 (0.3%) | 0/761 (0%) | ||
| Intestinal sepsis | 0/757 (0%) | 1/761 (0.1%) | ||
| Neutropenic sepsis | 0/757 (0%) | 2/761 (0.3%) | ||
| Balanoposthitis infective | 0/757 (0%) | 1/761 (0.1%) | ||
| Device related infection | 0/757 (0%) | 1/761 (0.1%) | ||
| Encephalitis | 1/757 (0.1%) | 0/761 (0%) | ||
| Enterocolitis bacterial | 0/757 (0%) | 1/761 (0.1%) | ||
| Fungal oesophagitis | 1/757 (0.1%) | 0/761 (0%) | ||
| Influenza | 0/757 (0%) | 1/761 (0.1%) | ||
| Pneumonia | 22/757 (2.9%) | 33/761 (4.3%) | ||
| Septic shock | 3/757 (0.4%) | 10/761 (1.3%) | ||
| Urosepsis | 4/757 (0.5%) | 1/761 (0.1%) | ||
| Abscess intestinal | 1/757 (0.1%) | 0/761 (0%) | ||
| Bacteraemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Bronchopneumonia | 0/757 (0%) | 1/761 (0.1%) | ||
| Gastrointestinal infection | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Pneumonia streptococcal | 0/757 (0%) | 1/761 (0.1%) | ||
| Staphylococcal sepsis | 0/757 (0%) | 2/761 (0.3%) | ||
| Anal abscess | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Appendicitis | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Clostridium difficile infection | 0/757 (0%) | 1/761 (0.1%) | ||
| Device related sepsis | 1/757 (0.1%) | 0/761 (0%) | ||
| Erysipelas | 0/757 (0%) | 1/761 (0.1%) | ||
| Infective exacerbation of chronic obstructive airways disease | 0/757 (0%) | 1/761 (0.1%) | ||
| Neutropenic infection | 3/757 (0.4%) | 3/761 (0.4%) | ||
| Perirectal abscess | 2/757 (0.3%) | 0/761 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Fracture | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Gastroenteritis radiation | 1/757 (0.1%) | 0/761 (0%) | ||
| Hip fracture | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Radiation proctitis | 0/757 (0%) | 4/761 (0.5%) | ||
| Venous injury | 0/757 (0%) | 1/761 (0.1%) | ||
| Accidental overdose | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Contusion | 1/757 (0.1%) | 0/761 (0%) | ||
| Femoral neck fracture | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Gastrointestinal anastomotic leak | 0/757 (0%) | 1/761 (0.1%) | ||
| Infusion related reaction | 1/757 (0.1%) | 0/761 (0%) | ||
| Joint injury | 1/757 (0.1%) | 0/761 (0%) | ||
| Multiple fractures | 1/757 (0.1%) | 0/761 (0%) | ||
| Tracheal obstruction | 1/757 (0.1%) | 0/761 (0%) | ||
| Upper limb fracture | 0/757 (0%) | 1/761 (0.1%) | ||
| Anastomotic leak | 0/757 (0%) | 1/761 (0.1%) | ||
| Clavicle fracture | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Femur fracture | 2/757 (0.3%) | 2/761 (0.3%) | ||
| Lower limb fracture | 0/757 (0%) | 1/761 (0.1%) | ||
| Thoracic vertebral fracture | 1/757 (0.1%) | 0/761 (0%) | ||
| Ulna fracture | 1/757 (0.1%) | 0/761 (0%) | ||
| Procedural complication | 1/757 (0.1%) | 0/761 (0%) | ||
| Rib fracture | 0/757 (0%) | 1/761 (0.1%) | ||
| Fall | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Spinal compression fracture | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Lumbar vertebral fracture | 1/757 (0.1%) | 0/761 (0%) | ||
| Overdose | 6/757 (0.8%) | 11/761 (1.4%) | ||
| Spinal fracture | 3/757 (0.4%) | 0/761 (0%) | ||
| Investigations | ||||
| Aspartate aminotransferase increased | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Bone marrow myelogram abnormal | 0/757 (0%) | 1/761 (0.1%) | ||
| Haemoglobin decreased | 3/757 (0.4%) | 9/761 (1.2%) | ||
| Neutrophil count | 1/757 (0.1%) | 0/761 (0%) | ||
| Neutrophil count decreased | 2/757 (0.3%) | 0/761 (0%) | ||
| Transaminases increased | 1/757 (0.1%) | 0/761 (0%) | ||
| Weight decreased | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Haemoglobin | 0/757 (0%) | 1/761 (0.1%) | ||
| Alanine aminotransferase increased | 0/757 (0%) | 1/761 (0.1%) | ||
| Clostridium test positive | 0/757 (0%) | 1/761 (0.1%) | ||
| Eastern Cooperative Oncology Group performance status worsened | 0/757 (0%) | 3/761 (0.4%) | ||
| Platelet count decreased | 1/757 (0.1%) | 0/761 (0%) | ||
| Urine output decreased | 0/757 (0%) | 1/761 (0.1%) | ||
| Blood creatinine increased | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Metabolism and nutrition disorders | ||||
| Malnutrition | 0/757 (0%) | 1/761 (0.1%) | ||
| Hyperkalaemia | 0/757 (0%) | 1/761 (0.1%) | ||
| Hypokalaemia | 2/757 (0.3%) | 3/761 (0.4%) | ||
| Dehydration | 11/757 (1.5%) | 21/761 (2.8%) | ||
| Hypercalcaemia | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Hyponatraemia | 3/757 (0.4%) | 2/761 (0.3%) | ||
| Tumour lysis syndrome | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Fluid overload | 0/757 (0%) | 1/761 (0.1%) | ||
| Hypomagnesaemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Hypophagia | 1/757 (0.1%) | 0/761 (0%) | ||
| Metabolic acidosis | 0/757 (0%) | 2/761 (0.3%) | ||
| Hypoglycaemia | 4/757 (0.5%) | 3/761 (0.4%) | ||
| Decreased appetite | 4/757 (0.5%) | 3/761 (0.4%) | ||
| Hyperglycaemia | 3/757 (0.4%) | 2/761 (0.3%) | ||
| Hypocalcaemia | 6/757 (0.8%) | 4/761 (0.5%) | ||
| Hypophosphataemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscle spasms | 0/757 (0%) | 1/761 (0.1%) | ||
| Neck pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Osteonecrosis | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Systemic lupus erythematosus | 1/757 (0.1%) | 0/761 (0%) | ||
| Fistula | 0/757 (0%) | 1/761 (0.1%) | ||
| Musculoskeletal pain | 3/757 (0.4%) | 1/761 (0.1%) | ||
| Osteonecrosis of jaw | 1/757 (0.1%) | 0/761 (0%) | ||
| Bone pain | 7/757 (0.9%) | 4/761 (0.5%) | ||
| Flank pain | 0/757 (0%) | 1/761 (0.1%) | ||
| Musculoskeletal chest pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Groin pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Hypercreatinaemia | 1/757 (0.1%) | 0/761 (0%) | ||
| Pain in extremity | 3/757 (0.4%) | 3/761 (0.4%) | ||
| Pathological fracture | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Spinal pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Arthralgia | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Back pain | 12/757 (1.6%) | 7/761 (0.9%) | ||
| Muscular weakness | 4/757 (0.5%) | 3/761 (0.4%) | ||
| Osteoarthritis | 0/757 (0%) | 1/761 (0.1%) | ||
| Rotator cuff syndrome | 0/757 (0%) | 1/761 (0.1%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Adenosquamous cell lung cancer | 1/757 (0.1%) | 0/761 (0%) | ||
| Neoplasm progression | 0/757 (0%) | 1/761 (0.1%) | ||
| Rectal adenocarcinoma | 1/757 (0.1%) | 0/761 (0%) | ||
| Renal neoplasm | 0/757 (0%) | 1/761 (0.1%) | ||
| Astrocytoma malignant | 1/757 (0.1%) | 0/761 (0%) | ||
| Cancer pain | 0/757 (0%) | 1/761 (0.1%) | ||
| Prostate cancer | 3/757 (0.4%) | 2/761 (0.3%) | ||
| Colorectal cancer | 0/757 (0%) | 1/761 (0.1%) | ||
| Malignant neoplasm progression | 1/757 (0.1%) | 0/761 (0%) | ||
| Basal cell carcinoma | 0/757 (0%) | 1/761 (0.1%) | ||
| Metastases to meninges | 1/757 (0.1%) | 0/761 (0%) | ||
| Metastatic neoplasm | 0/757 (0%) | 1/761 (0.1%) | ||
| Rectal cancer | 1/757 (0.1%) | 0/761 (0%) | ||
| Squamous cell carcinoma of skin | 0/757 (0%) | 1/761 (0.1%) | ||
| Squamous cell carcinoma of the oral cavity | 1/757 (0.1%) | 0/761 (0%) | ||
| Non-small cell lung cancer | 0/757 (0%) | 1/761 (0.1%) | ||
| Colorectal cancer recurrent | 1/757 (0.1%) | 0/761 (0%) | ||
| Meningioma | 1/757 (0.1%) | 0/761 (0%) | ||
| Metastatic squamous cell carcinoma | 0/757 (0%) | 2/761 (0.3%) | ||
| Prostate cancer metastatic | 10/757 (1.3%) | 9/761 (1.2%) | ||
| Metastasis | 2/757 (0.3%) | 2/761 (0.3%) | ||
| Nervous system disorders | ||||
| Carotid artery stenosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Nerve root compression | 0/757 (0%) | 1/761 (0.1%) | ||
| Paraparesis | 1/757 (0.1%) | 0/761 (0%) | ||
| Haemorrhage intracranial | 0/757 (0%) | 1/761 (0.1%) | ||
| IIIrd nerve disorder | 1/757 (0.1%) | 0/761 (0%) | ||
| Peripheral motor neuropathy | 4/757 (0.5%) | 1/761 (0.1%) | ||
| Aphasia | 0/757 (0%) | 1/761 (0.1%) | ||
| Cerebral haematoma | 0/757 (0%) | 1/761 (0.1%) | ||
| Cerebral ischaemia | 0/757 (0%) | 3/761 (0.4%) | ||
| Cerebrovascular accident | 4/757 (0.5%) | 2/761 (0.3%) | ||
| Depressed level of consciousness | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Headache | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Ataxia | 0/757 (0%) | 1/761 (0.1%) | ||
| Coma | 0/757 (0%) | 1/761 (0.1%) | ||
| Monoplegia | 1/757 (0.1%) | 0/761 (0%) | ||
| Neuralgia | 2/757 (0.3%) | 0/761 (0%) | ||
| Central nervous system haemorrhage | 0/757 (0%) | 1/761 (0.1%) | ||
| Cerebral haemorrhage | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Dysarthria | 1/757 (0.1%) | 0/761 (0%) | ||
| Motor dysfunction | 1/757 (0.1%) | 0/761 (0%) | ||
| Somnolence | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Ischaemic stroke | 0/757 (0%) | 1/761 (0.1%) | ||
| Peripheral sensory neuropathy | 0/757 (0%) | 1/761 (0.1%) | ||
| Syncope | 5/757 (0.7%) | 4/761 (0.5%) | ||
| Intracranial pressure increased | 0/757 (0%) | 1/761 (0.1%) | ||
| Seizure | 0/757 (0%) | 2/761 (0.3%) | ||
| Transient ischaemic attack | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Dizziness | 2/757 (0.3%) | 1/761 (0.1%) | ||
| Spinal cord compression | 6/757 (0.8%) | 4/761 (0.5%) | ||
| Psychiatric disorders | ||||
| Agitation | 0/757 (0%) | 1/761 (0.1%) | ||
| Disorientation | 1/757 (0.1%) | 0/761 (0%) | ||
| Mental status changes | 1/757 (0.1%) | 0/761 (0%) | ||
| Depression suicidal | 0/757 (0%) | 1/761 (0.1%) | ||
| Anxiety | 1/757 (0.1%) | 0/761 (0%) | ||
| Confusional state | 2/757 (0.3%) | 6/761 (0.8%) | ||
| Psychotic disorder | 0/757 (0%) | 1/761 (0.1%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 4/757 (0.5%) | 8/761 (1.1%) | ||
| Haemoglobinuria | 1/757 (0.1%) | 0/761 (0%) | ||
| Haemorrhage urinary tract | 0/757 (0%) | 2/761 (0.3%) | ||
| Hydronephrosis | 3/757 (0.4%) | 6/761 (0.8%) | ||
| Renal disorder | 0/757 (0%) | 1/761 (0.1%) | ||
| Bladder neck obstruction | 0/757 (0%) | 1/761 (0.1%) | ||
| Bladder obstruction | 3/757 (0.4%) | 3/761 (0.4%) | ||
| Renal colic | 0/757 (0%) | 1/761 (0.1%) | ||
| Urethral stenosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Renal impairment | 3/757 (0.4%) | 0/761 (0%) | ||
| Urinary bladder haemorrhage | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Nephrotic syndrome | 0/757 (0%) | 2/761 (0.3%) | ||
| Ureteric obstruction | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Ureteric stenosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Urinary bladder polyp | 1/757 (0.1%) | 0/761 (0%) | ||
| Urinary retention | 9/757 (1.2%) | 9/761 (1.2%) | ||
| Urinary tract obstruction | 2/757 (0.3%) | 3/761 (0.4%) | ||
| Bladder outlet obstruction | 0/757 (0%) | 1/761 (0.1%) | ||
| Dysuria | 1/757 (0.1%) | 0/761 (0%) | ||
| Haematuria | 18/757 (2.4%) | 10/761 (1.3%) | ||
| Renal failure | 5/757 (0.7%) | 5/761 (0.7%) | ||
| Obstructive uropathy | 1/757 (0.1%) | 0/761 (0%) | ||
| Urinary incontinence | 1/757 (0.1%) | 0/761 (0%) | ||
| Urogenital haemorrhage | 0/757 (0%) | 2/761 (0.3%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 1/757 (0.1%) | 0/761 (0%) | ||
| Prostatic obstruction | 0/757 (0%) | 1/761 (0.1%) | ||
| Penile pain | 1/757 (0.1%) | 0/761 (0%) | ||
| Oedema genital | 1/757 (0.1%) | 2/761 (0.3%) | ||
| Testicular mass | 1/757 (0.1%) | 0/761 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 10/757 (1.3%) | 21/761 (2.8%) | ||
| Hypoxia | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Pneumothorax | 0/757 (0%) | 2/761 (0.3%) | ||
| Productive cough | 0/757 (0%) | 1/761 (0.1%) | ||
| Alveolitis | 0/757 (0%) | 1/761 (0.1%) | ||
| Lung disorder | 0/757 (0%) | 1/761 (0.1%) | ||
| Cough | 1/757 (0.1%) | 3/761 (0.4%) | ||
| Interstitial lung disease | 0/757 (0%) | 2/761 (0.3%) | ||
| Pulmonary oedema | 0/757 (0%) | 2/761 (0.3%) | ||
| Respiratory failure | 2/757 (0.3%) | 7/761 (0.9%) | ||
| Dyspnoea exertional | 2/757 (0.3%) | 0/761 (0%) | ||
| Pleural effusion | 1/757 (0.1%) | 19/761 (2.5%) | ||
| Pneumonitis | 7/757 (0.9%) | 7/761 (0.9%) | ||
| Acute pulmonary oedema | 0/757 (0%) | 1/761 (0.1%) | ||
| Pulmonary embolism | 17/757 (2.2%) | 5/761 (0.7%) | ||
| Pulmonary hypertension | 0/757 (0%) | 2/761 (0.3%) | ||
| Pulmonary congestion | 0/757 (0%) | 1/761 (0.1%) | ||
| Pulmonary venous thrombosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Acute respiratory distress syndrome | 0/757 (0%) | 2/761 (0.3%) | ||
| Acute respiratory failure | 0/757 (0%) | 1/761 (0.1%) | ||
| Chronic obstructive pulmonary disease | 0/757 (0%) | 1/761 (0.1%) | ||
| Lung infiltration | 0/757 (0%) | 1/761 (0.1%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Peau d'orange | 0/757 (0%) | 1/761 (0.1%) | ||
| Rash | 0/757 (0%) | 1/761 (0.1%) | ||
| Pyoderma gangrenosum | 1/757 (0.1%) | 0/761 (0%) | ||
| Drug eruption | 1/757 (0.1%) | 0/761 (0%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 10/757 (1.3%) | 1/761 (0.1%) | ||
| Hypotension | 8/757 (1.1%) | 3/761 (0.4%) | ||
| Shock haemorrhagic | 1/757 (0.1%) | 0/761 (0%) | ||
| Venous thrombosis limb | 1/757 (0.1%) | 0/761 (0%) | ||
| Circulatory collapse | 0/757 (0%) | 1/761 (0.1%) | ||
| Haematoma | 0/757 (0%) | 1/761 (0.1%) | ||
| Aortic dissection | 1/757 (0.1%) | 0/761 (0%) | ||
| Haemorrhage | 1/757 (0.1%) | 1/761 (0.1%) | ||
| Vasculitis | 0/757 (0%) | 1/761 (0.1%) | ||
| Embolism | 1/757 (0.1%) | 0/761 (0%) | ||
| Infarction | 0/757 (0%) | 1/761 (0.1%) | ||
| Thrombosis | 0/757 (0%) | 2/761 (0.3%) | ||
| Vena cava thrombosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Venous thrombosis | 0/757 (0%) | 1/761 (0.1%) | ||
| Hypertension | 1/757 (0.1%) | 0/761 (0%) | ||
| Jugular vein thrombosis | 1/757 (0.1%) | 0/761 (0%) | ||
| Peripheral vascular disorder | 0/757 (0%) | 1/761 (0.1%) | ||
| Phlebitis | 2/757 (0.3%) | 0/761 (0%) | ||
| Thrombophlebitis superficial | 1/757 (0.1%) | 0/761 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Placebo | Dasatinib | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 701/757 (92.6%) | 716/761 (94.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 142/757 (18.8%) | 217/761 (28.5%) | ||
| Neutropenia | 67/757 (8.9%) | 79/761 (10.4%) | ||
| Eye disorders | ||||
| Lacrimation increased | 86/757 (11.4%) | 48/761 (6.3%) | ||
| Gastrointestinal disorders | ||||
| Dyspepsia | 59/757 (7.8%) | 50/761 (6.6%) | ||
| Stomatitis | 47/757 (6.2%) | 47/761 (6.2%) | ||
| Nausea | 231/757 (30.5%) | 288/761 (37.8%) | ||
| Abdominal pain | 67/757 (8.9%) | 66/761 (8.7%) | ||
| Diarrhoea | 312/757 (41.2%) | 414/761 (54.4%) | ||
| Vomiting | 117/757 (15.5%) | 166/761 (21.8%) | ||
| Constipation | 189/757 (25%) | 157/761 (20.6%) | ||
| General disorders | ||||
| Pain | 62/757 (8.2%) | 47/761 (6.2%) | ||
| Pyrexia | 71/757 (9.4%) | 132/761 (17.3%) | ||
| Mucosal inflammation | 52/757 (6.9%) | 70/761 (9.2%) | ||
| Oedema | 47/757 (6.2%) | 36/761 (4.7%) | ||
| Oedema peripheral | 207/757 (27.3%) | 162/761 (21.3%) | ||
| Fatigue | 329/757 (43.5%) | 334/761 (43.9%) | ||
| Chest pain | 34/757 (4.5%) | 49/761 (6.4%) | ||
| Asthenia | 143/757 (18.9%) | 163/761 (21.4%) | ||
| Infections and infestations | ||||
| Urinary tract infection | 67/757 (8.9%) | 73/761 (9.6%) | ||
| Investigations | ||||
| Haemoglobin decreased | 27/757 (3.6%) | 49/761 (6.4%) | ||
| Weight decreased | 77/757 (10.2%) | 121/761 (15.9%) | ||
| Weight increased | 64/757 (8.5%) | 36/761 (4.7%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 23/757 (3%) | 44/761 (5.8%) | ||
| Decreased appetite | 151/757 (19.9%) | 207/761 (27.2%) | ||
| Hyperglycaemia | 55/757 (7.3%) | 41/761 (5.4%) | ||
| Hypocalcaemia | 24/757 (3.2%) | 40/761 (5.3%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscle spasms | 42/757 (5.5%) | 15/761 (2%) | ||
| Musculoskeletal pain | 55/757 (7.3%) | 62/761 (8.1%) | ||
| Bone pain | 70/757 (9.2%) | 61/761 (8%) | ||
| Musculoskeletal chest pain | 40/757 (5.3%) | 35/761 (4.6%) | ||
| Pain in extremity | 128/757 (16.9%) | 115/761 (15.1%) | ||
| Myalgia | 54/757 (7.1%) | 50/761 (6.6%) | ||
| Arthralgia | 124/757 (16.4%) | 104/761 (13.7%) | ||
| Back pain | 194/757 (25.6%) | 148/761 (19.4%) | ||
| Muscular weakness | 51/757 (6.7%) | 38/761 (5%) | ||
| Nervous system disorders | ||||
| Headache | 65/757 (8.6%) | 82/761 (10.8%) | ||
| Dysgeusia | 147/757 (19.4%) | 165/761 (21.7%) | ||
| Neuropathy peripheral | 109/757 (14.4%) | 83/761 (10.9%) | ||
| Peripheral sensory neuropathy | 106/757 (14%) | 98/761 (12.9%) | ||
| Dizziness | 61/757 (8.1%) | 64/761 (8.4%) | ||
| Paraesthesia | 59/757 (7.8%) | 44/761 (5.8%) | ||
| Psychiatric disorders | ||||
| Insomnia | 95/757 (12.5%) | 76/761 (10%) | ||
| Renal and urinary disorders | ||||
| Haematuria | 44/757 (5.8%) | 46/761 (6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Dyspnoea | 127/757 (16.8%) | 154/761 (20.2%) | ||
| Cough | 112/757 (14.8%) | 137/761 (18%) | ||
| Epistaxis | 41/757 (5.4%) | 33/761 (4.3%) | ||
| Pleural effusion | 28/757 (3.7%) | 117/761 (15.4%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Nail disorder | 119/757 (15.7%) | 80/761 (10.5%) | ||
| Rash | 75/757 (9.9%) | 106/761 (13.9%) | ||
| Alopecia | 326/757 (43.1%) | 311/761 (40.9%) | ||
| Dry skin | 46/757 (6.1%) | 54/761 (7.1%) | ||
| Vascular disorders | ||||
| Hypertension | 42/757 (5.5%) | 22/761 (2.9%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00744497
Other Study ID Numbers:
- CA180-227
- 2008-000701-11
First Posted:
Sep 1, 2008
Last Update Posted:
Oct 17, 2016
Last Verified:
Aug 1, 2016