Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Androgens

Dasatinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Tablets, Oral, 100 mg or 70 mg, twice daily, treatment may continue until disease progression

dasatinib

Tablets, Oral, 100 mg, once daily (QD) treatment may continue until disease progression

Bristol-Myers Squibb

The purpose of this study is to learn if men with metastatic prostate cancer and rising Prostate Specific Antigen (PSA), who have been surgically castrated or are undergoing androgen deprivation with Luteinizing Hormone Releasing Hormone (LHRH) treatment, respond to dasatinib. The safety of this treatment will also be studied.

Phase II Study of Dasatinib (BMS-354825) for Androgen-deprived Progressive Prostate Cancer

Response = confirmed prostate specific antigen (PSA) response (decrease in PSA =\>50% from baseline), confirmed improved bone scan (disappearance of =\> 1 lesion, no new lesions, new pain not developing), confirmed complete response (CR: disappearance of all lesions) or confirmed partial response (PR: =\>30% in sum of longest diameter \[LD\] of all lesions compared to baseline sum LD), stable disease (SD: neither sufficient increase for progressive disease \[PD: =\>20% increase in sum of LD of all target lesions\] nor sufficient shrinkage for PR), based on Response Criteria in Solid Tumors \[RECIST\].

Response = confirmed PSA response (decrease in PSA =\>50% from baseline), confirmed improved bone scan (disappearance of =\> 1 lesion, no new lesions, new pain not developing), confirmed CR (disappearance of all lesions) or confirmed PR (=\>30% in sum of LD of all lesions compared to baseline sum LD), SD (neither sufficient increase for PD \[=\>20% increase in sum of LD of all target lesions\] nor sufficient shrinkage for PR), based on RECIST.

PSA is a marker of prostate cancer and a PSA response is defined as a decrease in the PSA value by at least 50% from baseline, for 2 successive evaluations, each at least 2 weeks apart, for a total of 3 measurements.

PSA is a marker of prostate cancer and a PSA response is defined as a decrease in the PSA value by at least 50% from baseline for 2 successive evaluations, each at least 2 weeks apart, for a total of 3 measurements.

PSA is a marker of prostate cancer. The duration of PSA response is measured from the time that the first of the 2 consecutive measurements met the criteria for confirmed PSA response, until the date of the first of the 3 consecutive measurements that confirm PSA progression, or the date of disease progression, or the date of death.

PSA is a marker of prostate cancer. PSA velocity measures the rate of change of PSA values. A decrease in PSA values and hence PSA velocity is an early indicator of potential anti-tumor activity.

PSA is a marker of prostate cancer. A decrease in PSA value is an early indicator of potential anti-tumor activity. Log (PSA) is assumed to have a linear relationship with time. The PSA log slope is defined as the slope of the log PSA line.

PSA is a marker of prostate cancer. PSA doubling time is defined as log 2 divided by the slope of the log PSA line. An increase in PSA doubling time indicates improvement in anti-tumor activity.

Tumor response was defined as the number of participants whose best response was CR or PR, per RECIST: CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD

Disease control rate is defined as the number of participants whose best response was CR, PR or SD, per RECIST: CR: disappearance of all target/non-target lesions; PR: \>= 30% decrease in the sum of the LDs of target lesions relative to the baseline sum LD; SD: neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR; PD: defined as appearance of new lesion/s, or \>=20% increase in the sum of the LD of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

An improved bone scan was defined as 1 or more of the following: disappearance of at least 1 lesion, no new lesions appearing since the most recent prior assessment, or new pain not developing in an area that was previously visualized. A response is considered confirmed if it is noted on 2 examinations at least 4 weeks apart.

Disease progression: progression of target lesions or unequivocal progression of non-measurable lesions/disease as evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI), not as evaluated by bone scan (non-measurable lesions included visceral and bone lesions), loss of PSA response (only for participants who achieved a PSA response) or Investigator-defined clinical progression based on physical examination, history, symptoms, and ECOG-PS. For participants who did not progress or die, date of last PSA measurement or tumor assessment was used, whichever occurred first.

Measured from date of first dose to date of first 3 consecutive measurements that confirm PSA progression, date of disease progression,or death date.Disease progression:progression of target lesions or unequivocal progression of non-measurable lesions/disease as evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI),loss of PSA response or Investigator-defined clinical progression based on physical examination,history,symptoms,and ECOG-PS.For participants who did not progress or die,date of last PSA measurement or tumor assessment was used, whichever occurred first.

FAPSI-8:symptom index of important clinician-rated symptoms/concerns to monitor when assessing value of treatment for advanced prostate cancer. Participants respond to each item on a 5-point Likert-type scale from 0 (not at all) to 4 (very much). GP1:I have lack of energy, GP4:I have pain, GE6:I worry that my condition will get worse, C2: I am losing weight, P2:I have certain areas in my body where I experience significant pain,P3:My pain keeps me from doing things I want to do, P7:I have difficulty urinating, P8:My problems with urinating limit my activities.

The FAPSI-8 is a symptom index comprised of the most important clinician-rated symptoms or concerns to monitor when assessing the value of treatment for advanced prostate cancer. It includes 8 items developed to measure symptoms/concerns specific to prostate cancer such as fatigue, pain (3-items), weight loss, difficulty with urination (2-items) and concerns about the condition becoming worse. Participants respond to each item on a 5-point Likert-type scale from 0 (not at all) to 4 (very much).

FAPSI-8:index of symptoms/concerns when assessing value of treatment for advanced prostate cancer.Participants respond to each item on 5-point Likert-type scale:0 (not at all) to 4 (very much).GP1:I have lack of energy,GP4:I have pain,GE6:I worry that my condition will get worse,C2:I am losing weight,P2:I have certain areas in my body where I experience significant pain,P3:My pain keeps me from doing things I want to do,P7:I have difficulty urinating,P8:My problems with urinating limit my activities. The number of participants for whom these data are available is too small for analysis.

AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to any AEs were recorded.

Drug-related AEs are those events with a relationship to the study therapy of certain; probable; possible; or missing. Drug-related SAEs are those events with any relationship to the study therapy. Drug-related AEs were graded using the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0: Grade 1=mild, 2=moderate, 3=severe, 4=life threatening, 5=death. Participants who discontinued the study due to any drug-related AEs were also recorded.

Abnormalities were graded per the NCI CTC, version 3.0 criteria (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: Hemoglobin: Grade 3:6.5 - \<8.0g/dL, Grade 4: \<6.5g/dL. Platelets: Grade 3: 25.0 - \<50.0\*10\^9/L, Grade 4: \<25.0\*10. Absolute Neutrophil Count (ANC): Grade 3: 0.5 - \<1.0\*10\^9/L, Grade 4: \<0.5\*10\^9/L. Leukocytes: Grade 3: 1.0 - \<2.0\*10\^9/L, Grade 4: \<1.0\*10\^9/L.

Abnormalities were graded according to the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase: Grade 3: 5.0-20.0 \* ULN (upper limit of normal), Grade 4: \>20.0 \* ULN; calcium: Grade 3: 6.0-\<7.0 or \>12.5-13.5 mg/dL, Grade 4: \<0.6-\>13.5 mg/dL; bilirubin: Grade 3: \>3-10 \* ULN, Grade 4: \>10 \* ULN.

Abnormalities were graded per the NCI CTC, version 3.0 (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening). Grade 3 and 4 criteria are as follows: phosphorous: Grade 3: 1.0-\<2.0 mg/dL, Grade 4: \<1.0 mg/dL; sodium: Grade 3: 120-\<130 or \>155-160mEq/L, Grade 4: \<120 or \>160 mEq/L; creatinine: Grade 3: \>3.0-6.0 \* ULN, Grade 4: \>6.0 \* ULN; potassium: Grade 3: 2.5 -\<3.0 or \>6.0 -7.0 mEq/L, Grade 4: \< 2.5 or \>7.0 mEq/L.

LDH is a laboratory safety parameter. Normal ranges for LD vary with both age and disease status, and another reason for variation in upper limit of normal (ULN) and lower limit of normal (LLN) is that LD was measured via a local (versus a standardized) laboratory. It is therefore not possible to provide one ULN and LLN for the population.

Participants' urine samples were tested for the presence of blood, glucose and protein. If these substances were present in a participant's urine, the results were given as "positive".

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. QTc is the QT interval corrected for heart rate. A prolonged QT interval is a risk factor for ventricular tachyarrhythmias and sudden death.

uNTx is a measure of bone metabolism. A decrease in the marker relative to baseline indicates a decrease in bone metabolism.

uNTx is a measure of bone metabolism. uNTx response is defined for participants with baseline uNTx above ULN. It is defined as either on-study uNTx values decreasing to within normal limits or 35% or more decrease in uNTx from baseline, whichever happens first.

uNTx is a measure of bone metabolism.The median number of months of uNTx response was calculated for participants with baseline uNTx =\< ULN and uNTx progression during treatment, from first dose of dasatinib to uNTx progression.For participant with baseline uNTx above ULN, it was time from uNTx response to uNTx progression.For participants with baseline uNTx equal to or below ULN or uNTx response and no uNTx progression, the date of last uNTx assessment was used. Duration of uNTx response was not defined for participants with baseline value greater than ULN who never achieved uNTx responses.

BAP is a measure of bone metabolism. A decrease in BAP relative to the baseline indicates decrease in bone metabolism.

BAP is a measure of bone metabolism. A decrease in BAP relative to baseline indicates a decrease in bone metabolism.

BAP is a measure of bone metabolism. A BAP response is calculated for participants with a baseline BAP value \> ULN. It is defined as on-study BAP values within normal limits.

The median number of months of the BAP response was calculated for participants with baseline BAP \<= ULN, from first dose of dasatinib to the first time BAP is above ULN. For participants with baseline BAP \> ULN, it was the time from BAP response to the first time BAP was above ULN. For participants with baseline BAP =\< ULN or BAP, and no BAP above ULN, last BAP assessment date was used. The median number of months of response was not defined for participants with baseline value \> ULN, that never achieved BAP response.

Mean plasma concentration was obtained directly from the concentration-time data.

Participants were administered an oral dose of 100 mg dasatinib tablet QD. Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Dasatinib 100 mg Once Daily (QD)

Participants were administered an oral dose of 100 mg dasatinib tablet BID for a total daily dose (TDD) of 200 mg which was later decreased to 70 mg BID for a TDD of 140 mg. Of the 47 treated participants in the BID group, 25 received 100 mg and 22 received 70 mg of dasatinib as their starting doses. Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Dasatinib 100 mg or 70 mg Twice Daily (BID)

Total

Age Continuous

< 65 years

>=65 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black/African American

Hispanic

Race/Ethnicity, Customized

0=normal activity

1=symptoms, but fully ambulatory

2=symptomatic, but in bed < 50% of the day.

3=needs to be in bed >50% of day, not bedridden

4=unable to get out of bed

5=dead

The ECOG PS is used to assess disease severity. A score of 0 is normal activity; 1 is symptoms, but fully ambulatory; 2 is symptomatic, but in bed \< 50% of the day; 3 is needs to be in bed \> 50% of the day, but not bedridden; 4 is unable to get out of bed; 5 is dead.

Eastern Cooperative Oncology Group (ECOG)Performance Status (PS)

Height continuous

Weight continuous

Total Score

FACT Advanced Prostate Symptom Index (FAPSI) -8 Score from baseline

< 60 nanomol (nmol)/mmol creatinine

>= 60 nmol/mmol creatinine

Unknown uNTx value

uNTx is a measure of bone metabolism decrease in the marker relative to baseline indicates a decrease in bone metabolism.

Urinary N-telopeptide (uNTx)Value from Baseline

High >41.3 U/L

Low <15 U/L

Normal 15-41.3 U/L

Unknown

Bone-specific Alkaline Phosphatase (BAP) Value from baseline

BMS Study Director

Number of Participants With a Response

Percentage of Participants With a Response

All PSA response-evaluable participants: participants who had pre-treatment PSA measurements and at least 2 on-study PSA measurements.

Number of Participants With a Decrease in PSA by at Least 50% From Baseline

Percentage of Participants With a Decrease in PSA by at Least 50% From Baseline

Participants with a decrease in PSA by at least 50% from baseline

Number of Months of Decrease in PSA by at Least 50% From Baseline

All PSA response-evaluable participants: participants who had 2 or more pre-treatment PSA measurements and at least 2 on-study PSA measurements.

Number of Participants With Decrease in PSA Velocity

Number of Participants With Decrease in PSA Log Slope

All PSA response-evaluable participants: participants who had 2 or more pre-treatment PSA measurements and at least 2 on-study PSA measurements and positive log slope pre-treatment and on-study measurements.

Number of Participants With Increase in PSA Doubling Time

Number of Participants With CR or PR

Number of Participants With CR, PR or SD

Number of Participants With a Confirmed Improved Bone Scan

Participants with confirmed improved bone scan.

Percentage of Participants With Confirmed Improved Bone Scan

Number of Participants With Disease Progression

Median Number of Months to Disease Progression

Median Change From Baseline in Individual FAPSI Scores at Week 12

Week 12 (n=26, 29)

Week 24 (n=14, 6)

Week 36 (n=4, 5)

Median Change From Baseline in Total FAPSI-8 Scores at Weeks 12, 24 and 36

Median Change From Baseline in Individual FAPSI Scores at Week 24

All treated participants. The number of participants for whom this data are available is too small for analysis.

Median Change From Baseline in Individual FAPSI Scores at Week 36

Deaths

SAEs

All AEs Leading to Discontinuation

Number of Participants Who Died, Experienced Serious Adverse Events (SAEs), Adverse Events (AEs) or Discontinuations Due to AEs

Drug-related SAEs

Drug-related AEs

Drug-related Grade 3-4 AEs

Drug-related AEs Leading to Discontinuation

Number of Participants Who Experienced Drug-related SAEs, Drug-related AEs, Drug-related Grade 3/4 AEs and Discontinuations Due to Drug-related AEs.

Absolute Neutrophil Count (ANC)

Hemoglobin

Platelet Count

Leukocytes

Number of Participants With Grade 3-4 Hematology Abnormalities

Alanine Aminotransferase

Aspartate Aminotransferase

Alkaline Phosphatase

Bilirubin

Hypercalcemia

Hypocalcemia

Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Alanine Aminotransferase, Aspartate Aminotransferase, Alkaline Phosphatase, Bilirubin and Calcium

Creatinine

Hyperkalemia

Hypokalemia

Hypernatremia

Hyponatremia

Phosphorus, Inorganic

Number of Participants With Grade 3-4 Serum Chemistry Abnormalities in Creatinine, Potassium, Sodium and Phosphorous

Number of Participants With Abnormal Lactate Dehydrogenase (LD)

Blood

Glucose

Protein

Number of Participants With Positive Urinalysis

Number of Participants With QTc Prolongation

0-35 percent decrease

>35-70 percent decrease

>70 percent decrease

No change or increase

All treated participants who had a baseline uNTx value \<=ULN and at least 1 on-study value.

Number of Participants With a Baseline uNTx Value <=ULN, With a Decrease, Increase or no Change in uNTx

All treated participants who had a baseline uNTx value \>ULN and at least 1 on-study value.

Number of Participants With a Baseline uNTx Value >ULN, With a Decrease, Increase or no Change in uNTx

Participants with a baseline uNTx value \> ULN and at least 1 on-study value.

Number of Participants With a uNTx Response

Participants who demonstrated a uNTx response.

Median Number of Months of uNTx Response

All treated participants who had a baseline BAP value \<=ULN and at least 1 on-study value.

Number of Participants With a Baseline BAP Value <= ULN, With a Decrease, Increase or no Change in BAP

All treated participants who had a baseline BAP value \>ULN and at least 1 on-study value.

Number of Participants With a Baseline BAP Value > ULN, With a Decrease, Increase or no Change in BAP

Participants with a baseline BAP value \> ULN and at least 1 on-study value.

Number of Participants With BAP Response

Participants who demonstrated a BAP response

Median Number of Months of BAP Response

0 hour (n=39,18,1)

1hour (n=41,19,1)

3 hour (n=41,19,1)

6 hour (n=41,18,1)

12 hour (n=30,12,1)

Participants were administered an oral dose of 100 mg dasatinib tablet QD (100 dose). Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Participants were administered an oral dose of 100 mg dasatinib tablet BID for a total daily dose (TDD) of 200 mg (100 dose). Of the 47 treated participants in the BID group, 25 received 100 mg of dasatinib as their starting dose. Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Dasatinib 100 mg Twice Daily (BID)

Participants were administered an oral dose of 100 mg dasatinib tablet BID for a total daily dose (TDD) of 70 mg BID for a TDD of 140 mg (100 dose). Of the 47 treated participants in the BID group, 22 received 70 mg of dasatinib as their starting dose. Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Dasatinib 70 mg BID

All available concentration-time data from participants who received at least 1 dose of dasatinib. The 'n' is signifying those who were evaluated for this measure at timepoint for each group respectively. Data are split by actual dose administered. If there was dose modification, participant was grouped according to dose given on PK collection day.

Mean Plasma Concentration at 100 mg Dasatinib Dose (Week 2)

0 hour (n=31,8,1)

1hour (n=36,9,1)

3 hour (n=36,9,1)

6 hour (n=36,9,1)

12 hour (n=26,8,1)

Mean Plasma Concentration at 100 mg Dasatinib Dose (Week 6)

0 hour (n=1,1,17)

1hour (n=1,1,20)

3 hour (n=1,1,20)

6 hour (n=1,1,19)

12 hour (n=1,1,18)

Participants were administered an oral dose of 100 mg dasatinib tablet QD (70 dose). Participants continued to receive the study drug as long as tolerated or until progressive disease (PD), defined as appearance of new lesion/s, or \>=20% increase in the sum of the longest diameter (LD) of target lesions, relative to the smallest sum LD recorded since treatment start, or unequivocal progression of existing non-target lesions.

Spots Global Cancer Trial Database for Phase II Study of Dasatinib (BMS-354825) for Androgen-deprived Progressive Prostate Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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