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

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Hormones

Dasatinib

Tubulin Modulators

Antimitotic Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants received dasatinib, 50 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 60 mg/m\^2.

Participants received dasatinib, 50 mg administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Participants received dasatinib, 70 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Participants received dasatinib, 100 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Participants received dasatinib, 120 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2.

Tablets, Oral, 50, 70, 100, or 120 mg once daily; treatment may continue until disease progression

Infusion, 60 or 75 mg/m\^2, administered every 3 weeks.

Bristol-Myers Squibb

The purpose of this study is to find the recommended doses of dasatinib and docetaxel given in combination to men with metastatic hormone refractory prostate cancer and to assess the pharmacokinetic interactions between the 2 drugs.

Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer

Phase I/II Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer

MTD was defined by dose-limiting toxicity (DLT) criteria. DLT was defined as grade 4 neutropenia causing treatment interruption for \>14 days, febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with a bleeding episode requiring platelet transfusion, nausea and/or vomiting despite medical intervention/prophylaxis causing treatment interruption for \>14 days, grade 3-4 asthenia/fatigue, any other grade \>=3 nonhematologic toxicity except alopecia or transient arthralgia/myalgia (unless unresponsive to intervention), or interruption of study drug for \>14 days due to toxicity. When defined, the MTD would serve as recommended Phase 2 dose of each drug in the combination of oral dasatinib and intravenous docetaxel.

Because no dose-limiting toxicities occurred, the recommended dose of dasatinib used in Phase 2 was based on findings from ongoing studies in chronic myelogenous leukemia and experience from the previous Phase 2 study of single-agent dasatinib in chronic refractory prostate cancer. The recommended Phase 2 dose of docetaxel (75 mg/m\^2) was based on the docetaxel package insert.

PSA response rate is defined as a decrease of \>=50% in PSA levels from baseline, sustained for at least 6 weeks and confirmed by at least 2 measurements

Duration of response is computed for participants with confirmed PSA response. It is measured in months from the time of the first of 2 consecutive measurements meeting the criteria for confirmed PSA response to the date of the first of 3 consecutive measurements that confirm PSA progression, the date of disease progression, or the date of death. Participants who neither progressed (PSA or disease) nor died were censored on the date of their last PSA assessment. PSA response is defined as a decrease of \>=50% in PSA levels from baseline, sustained for at least 6 weeks and confirmed by at least 2 measurements. PSA progression is defined as 3 consecutive increases in PSA from baseline or nadir, each measurement at least 1 week apart. The final confirming PSA measurement had to be ≥5ng/mL higher than baseline or nadir and also represent at least a 50% increase from baseline or nadir (ie, the value is ≥1.5\*baseline or nadir PSA).

PFS defined as time in months from the first dosing date to the date of disease progression or the date of death. Patients who neither progressed nor died were censored on the date of their last on-study prostate specific antigen (PSA) measurement, tumor assessment, or radionuclide bone scan assessment (whichever occurred last). Disease progression defined as either of the following: progression on radionuclide bone scan, death, or at least 2 of the following:

tumor progression, as defined by modified Response Evaluation Criteria in Solid Tumors; PSA progression; or investigator-defined clinical progression based on physical examination, history, symptoms, and performance status.

Objective response rate is defined as the percentage of participants who have achieved best responses of confirmed Complete Response (CR) or Partial Response (PR) where confirmed requires repeat evaluations for a minimum of 4 weeks after the criteria for response are first met. RECIST: CR=disappearance of clinical and radiologic evidence of target lesions; PR=a 30% or greater decrease in the sum of the longest diameter (LD) of all lesions in reference to the baseline sum LD.

RECIST for target lesions: Complete Response (CR)=disappearance of clinical and radiologic evidence of target lesions. Partial Response (PR)=a 30% or greater decrease in the sum of the longest diameter (LD) of all lesions in reference to the baseline sum LD. Stable disease (SD)=neither sufficient increase to qualify for Progressive Disease (PD) nor sufficient shrinkage to qualify for PR.

PD=a 20% or greater increase in the sum of LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline; unequivocal progression of nonmeasurable disease/lesions as evaluated by CT scan or MRI (not as evaluated by radionuclide bone scan) and/or new lesions are present.

To qualify as SD, patients had to exhibit SD for a minimum of 18 weeks. Those with evaluations noted as SD prior to 18 weeks and discontinued were reported as no change.

Stable=no new lesions appeared at any 6-week assessment or new pain was not developed in an area that was previously visualized for a minimum of 18 weeks; no change=stable disease prior to 18 weeks and then discontinued treatment; progression=2 or more new areas of focal uptake or new adverse clinical symptoms in an area previously visualized; improved=disappearance of at least 1 lesion, no new lesions appearing since the most recent prior assessment, and new pain not developing in an area that was previously visualized.

Improvement=disappearance of at least 1 lesion, no new lesions appearing since the most recent prior assessment, and new pain not developing in an area that was previously visualized

The BPI-sf assessed intensity of pain in the last 24 hours as well as impact of pain on daily functions. Patients rated the severity of their pain at its worst, least, and average in the last 24 hours using an 11-point rating scale with endpoints of no pain (0 points) and pain as bad as you can imagine (11 points). They were asked to rate their present pain and pain at the time they completed the BPI-sf. Using an 11-point rating scale with endpoints of does not interfere (0 points) and completely interferes (11 points), the BPI-sf similarly assessed to what extent pain interfered with mood, walking, general activity, work, relations with others, sleep, and enjoyment of life. The BPI-sf also asked patients to mark the location of their pain on a body drawing and included other questions about pain treatment and the extent of pain relief. The BPI-sf was collected in the Phase 2 portion of the study only. For on-treatment visits, the BPI-sf was completed prior to the docetaxel infusion.

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. Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening or disabling, Grade 5=Leading to death.

ULN=upper limit of normal. Graded by Common Toxicity Criteria: 1 (least severe) to 4 (life threatening ). Absolute neutrophil count (\*10\^9/L), Grade 3, \<1.0-0.5; Grade 4, \<0.5. Hemoglobin (mmol/L), Grade 3, \<4.9-4.0; Grade 4, \<4.0. Platelets (\*10\^9/L), Grade 3, \<50.0-25.0; Grade 4, \<25.0. Leukocytes (\*10\^9/L) Grade 3, \<2.0-1.0; Grade 4, \<1.0. ALP, ALT, and AST (\*ULN), Grade 3, \>5.0-20.0; Grade 4, \>20.0. Total bilirubin (\*ULN), Grade 3, \>3.0-10.0; Grade 4, \>10.0. Creatinine (\*ULN), Grade 3, \>3.0-6.0; Grade 4, \>6.0. Hypercalcemia (mmol/L), Grade 3, \>3.1-3.4; Grade 4, \>3.4. Hypocalcemia mmol/L), Grade 3, \<1.75-1.5; Grade 4, \<1.5. Hyperkalemia (mmol/L), Grade 3, \>6.0-7.0; Grade 4, \>7.0. Hypokalemia (mmol/L), Grade 3, \<3.0-2.5; Grade 4, \<2.5. Hypernatremia (mmol/L), Grade 3, \>155-160; Grade 4, \>160. Hyponatremia (mmol/L), Grade 3, \<130-120; Grade 4, \<120. Phosphorus (mmol/L), Grade 3, \<0.6-0.3; Grade 4, \<0.3. Prothrombin time (seconds), Grade 3, \>2.0; Grade 4, not defined.

Dasatinib, 100 mg + Docetaxel, 75 mg/m^2

Dasatinib, 120 mg + Docetaxel, 75 mg/m^2

Dasatinib, 50 mg + Docetaxel, 60 mg/m^2

Dasatinib, 50 mg + Docetaxel, 75 mg/m^2

Dasatinib, 70 mg + Docetaxel, 75 mg/m^2

Participants received dasatinib, 50 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 60 mg/m\^2. Provided no dose-limiting toxicities occurred, at least 3 participants received treatment in each arm.

Participants received dasatinib, 50 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2. Provided no dose-limiting toxicities occurred, at least 3 participants received treatment in each arm.

Participants received dasatinib, 70 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2. Provided no dose-limiting toxicities occurred, at least 3 participants received treatment in each arm.

Participants received dasatinib, 100 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2. Provided no dose-limiting toxicities occurred, at least 3 participants received treatment in each arm.

Participants received dasatinib, 120 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 75 mg/m\^2. Provided no dose-limiting toxicities occurred, at least 3 participants received treatment in each arm.

Total

<65 years

>=65 years

Age, Customized

Sex: Female, Male

Black or African American

White

Other

Race/Ethnicity, Customized

Hispanic/Latino

Not Hispanic/Latino

All patients who received at least 1 dose of dasatinib

Bristol-Myers Squibb Study Director

All patients who received dasatinib, 100 mg + docetaxel, 75 mg/m\^2

Percentage of Participants With a Prostate Specific Antigen (PSA) Response

Participants received dasatinib as 50, 70, 100, or 120 mg administered orally once daily with docetaxel, administered every 3 weeks as an infusion at 60 or 75 mg/m\^2. A standard 3+3 design was used, in which 3-6 patients were exposed to a dose level combination. Using a dose escalation scheme, the first 3-6 patients received the lower dose level combination. Escalation to the next dose level combination for another set of 3-6 patients was initiated if no dose-limiting toxicities (DLTs) were observed. If 2 or more DLTs were observed for a dose level combination, the MTD was defined as the previous dose level combination.

All Treated (Phase 1)

All patients who received at least 1 dose of dasatinib in Phase 1

Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel

All participants who received dasatinib, 100 mg + docetaxel, 75 mg/m\^2 and who had a PSA response

Duration of Prostate Specific Antigen (PSA) Response

Number of Months of Progression-free Survival (PFS)

Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

Complete response

Partial response

Stable disease

No change

Progressive disease

Not evaluable

Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)

Participants received dasatinib as 50, 70, 100, or 120 mg administered orally once daily with docetaxel, administered every 3 weeks as an infusion at 60 or 75 mg/m\^2. A standard 3+3 design was used, in which 3-6 patients were exposed to a dose level combination. Using a dose escalation scheme, the first 3-6 patients received the lower dose level combination. Escalation to the next dose level combination for another set of 3-6 patients was initiated if no dose-limiting toxicities (DLTs) were observed. If, for a dose level combination, 2 or more DLTs were observed, the maximum tolerated dose was defined as the previous dose level combination.

Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2

Improved

Stable

Progression

Number of Participants by Best On-study Bone Scan Assessment From Baseline

Percentage of Participants With Improvement on Bone Scan

Baseline: Average of pain (n=18)

Baseline: Average of pain interference (n=18)

Cycle 2: Average of pain (n=11)

Cycle 2: Average of pain interference (n=11)

Cycle 3: Average of pain (n=7)

Cycle 3: Average of pain interference (n=7)

Cycle 4: Average of pain (n=10)

Cycle 4: Average of pain interference (n=10)

Cycle 5: Average of pain (n=5)

Cycle 5: Average of pain interference (n=5)

Cycle 6: Average of pain (n=9)

Cycle 6: Average of pain interference (n=9)

Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 (Phase 2 )

All patients who received dasatinib, 100 mg + docetaxel, 75 mg/m\^2, in the Phase 2 portion of the study and completed the BPI-sf at baseline. n=evaluable participants in that cycle.

Baseline Scores and Changes in Pain Intensity From Baseline on the Brief Pain Inventory Short Form (BPI-sf) Scores Through Cycle 6

Deaths

SAEs

Drug-related SAEs

Drug-related AEs

Drug-related AEs leading to discontinuation

Drug-related Grade 3 or 4 AEs

Participants received dasatinib, 50, 70, 100, or 120 mg, administered orally once daily. Docetaxel was administered every 3 weeks as an infusion at 60 or 75 mg/m\^2.

All Treated

All participants who received at least 1 dose of dasatinib

Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), Drug-related AEs Leading to Discontinuation, and Drug-related Grade 3 or 4 AEs in the Overall Population

Number of Participants With Death as Outcome, Drug-related Serious Adverse Events (SAEs), Drug-related Adverse Events (AEs), Drug-related AEs Leading to Discontinuation, and Drug-related Grade 3 or 4 AEs in the Phase 2 Cohort

AUC(0-10) (n=3, 1, 3, 28, 3)

AUC(tau) (n=3, 1, 3, 21, 3)

All patients who received at least 1 dose of dasatinib; n=number of patients who were evaluable

Area Under the Concentration-time Curve (AUC) From 0 to 10 Hours Postdose (AUC [0-10])and AUC in 1 Dosing Interval, From Time 0 to 24 Hours (AUC[Tau])of Dasatinib Coadministered With Docetaxel

Dasatinib (n=3, 1, 3, 29, 3)

Docetaxel (n=3, 3, 3, 34, 3)

Maximum Observed Plasma Concentration (Cmax) of Dasatinib and of Docetaxel

Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity (AUC[Inf]) of Docetaxel

Absolute neutrophil count

Hemoglobin

Platelet count

Leukocytes

Alanine aminotransferase (ALT)

Aspartate aminotransferase (AST)

Alkaline phosphatase (ALP)

Total bilirubin

Hypercalcemia

Hypocalcemia

Creatinine

Hyperkalemia

Hypokalemia

Hypernatremia

Hyponatremia

Phosphorus, inorganic

Prothrombin time

All participants who received at least 1 dose of study drug

Spots Global Cancer Trial Database for Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial