Clinical trial NCT00439270: Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer
Official title: Phase I/II Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Metastatic Prostate Cancer
Keywords: Metastatic hormone refractory prostate cancer
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2007-02-23
Enrollment: 49
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate that was clinically refractory to hormone therapy
* Eastern Cooperative Oncology Group performance status of 0 - 2
* Evidence of progressive metastatic disease at time of enrollment
* Measurable disease on either computer tomography scan or magnetic resonance imaging or positive bone scan with any level of serum prostate specific antigen (PSA) ≥5 ng/ml. Patients with PSA ≥5 ng/ml only and no other radiographic evidence of metastatic prostate cancer were not eligible
* Evidence of progressive disease since the most recent change in therapy. Progressive disease was defined as any one of the following:

  * Objective disease progression: Objective evidence of increase in radiographic lesions or the appearance of 1 or more new lesions
  * Bone scan progression: Appearance of either of the following: 2 or more new lesions on bone scan attributable to prostate cancer or 1 new lesion on bone scan attributable to prostate cancer in conjunction with a rising PSA
  * PSA progression: 2 consecutively rising PSA levels (≥5 ng/mL) separated by 2 weeks with a testosterone concentration of ≤50 ng/dL at 2 week intervals
* Serum testosterone levels ≤50 ng/dL, determined within 2 weeks prior to starting treatment
* Maintaining castrate status: patients who had not undergone surgical orchiectomy must have continued on medical therapies, such as gonadotropin-releasing hormone analogs, to maintain castrate levels of serum testosterone. Those receiving an antiandrogen as part of their first-line hormonal therapy must have shown progression of disease off of the antiandrogen prior to enrollment (6 weeks withdrawal for bicalutamide; 4 weeks for flutamide)

Key Exclusion Criteria:

* Sexually active fertile men not using effective birth control if their partners were women of child-bearing potential
* Known brain metastases
* Clinically-significant cardiovascular disease, including myocardial infarction or ventricular tachyarrhythmia within 6 months; prolonged heart rate-corrected QT interval (QTc) \>450 msec; ejection fraction \<40%, or major conduction abnormality (unless a cardiac pacemaker was present)
* Pleural or pericardial effusion, due to concerns that the combination of docetaxel and dasatinib could worsen these events
* Uncontrolled intercurrent illness including, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social situations that limit compliance with study requirements
* Participants were permitted to continue on a daily multivitamin but all other herbal, alternative, and food supplements must have been discontinued before enrollment into the study
* Ketoconazole must have been discontinued 4 weeks prior to enrollment
* Patients were not permitted to receive radioactive bone targeting agents, such as Strontium or Samarian ,while on study treatment
* The following restrictions on prior therapy for metastatic disease applied:

  * One chemotherapy regimen was permitted as long as docetaxel resistance or intolerance was not demonstrated. Docetaxel resistance was defined as objective disease progression or confirmed PSA progression during docetaxel therapy or within 3 months of treatment completion. Docetaxel intolerance was defined as toxicity requiring docetaxel interruption \>4 weeks or dose modification below approved doses
  * No more than 1 prior course of palliative radiotherapy
  * Up to 1 prior treatment with a nonchemotherapeutic agent was permitted as treatment for metastatic prostate cancer
  * No prior radioisotope therapy with Strontium-89, Samarium, or similar agents
  * No limitation on prior hormonal therapy
  * QTc prolonging agents strongly associated with Torsade de Pointes arrhythmia

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel
timeFrame: From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)
measure: Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2
timeFrame: From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)
Secondary outcomes:
measure: Percentage of Participants With a Prostate Specific Antigen (PSA) Response
timeFrame: At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment (up to 51.6 months)
measure: Duration of Prostate Specific Antigen (PSA) Response
timeFrame: At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment
measure: Number of Months of Progression-free Survival (PFS)
timeFrame: Patients with an event: time from first dose to disease progression or death, whichever occurs first. Patients without an event: time to last on-study PSA measurement, tumor assessment, or radionuclide bone scan assessment, whichever occurs last
measure: Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)
measure: Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)
measure: Number of Participants by Best On-study Bone Scan Assessment From Baseline
timeFrame: From Day 1 of therapy to last bone scan assessment (up to 51.6 months)
measure: Percentage of Participants With Improvement on Bone Scan
timeFrame: From Day 1 of therapy to last bone scan assessment (up to 51.6 months)
measure: Baseline Scores and Changes in Pain Intensity From Baseline on the Brief Pain Inventory Short Form (BPI-sf) Scores Through Cycle 6
timeFrame: At pretreatment visit and on Day 1 of Cycles 2 through 6, then Day 1 of every other cycle, at end of treatment, and at follow-up visit
measure: 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
timeFrame: From first dose Day 1 through at least 30 days after last dose of either dasatinib or docetaxel, whichever was later (up to approximately 49 months)
measure: 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
timeFrame: From first dose Day 1 through at least 30 days after last dose of either dasatinib or docetaxel, whichever was later (up to approximately 49 months)
measure: 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
timeFrame: Cycle 1, Day 14 at 0, 0.5 , 1, 2, 3, 4, 7, 10, and 24 hours postdose
measure: Maximum Observed Plasma Concentration (Cmax) of Dasatinib and of Docetaxel
timeFrame: Docetaxel: Cycle 1, Day 1 at 0, 0.5, 1, 1.25, 1.5, 2, 3, 4, 7, 10, 24, and 48 hours postdose; dasatanib: Cycle 1, Day 14 at 0, .5, 1, 2, 3, 4, 7, 10, and 24 hours postdose
measure: Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity (AUC[Inf]) of Docetaxel
timeFrame: Cycle 1, Day 1 at 0, 0.5, 1, 1.25, 1.5, 2, 3, 4, 7, 10, 24, and 48 hours postdose
measure: Number of Participants Meeting the Criteria for On-study Abnormal Results Grade 3-4 of Clinical Laboratory Tests
timeFrame: From Day 2 of Cycle 1 to up to 30 days after last dose of study drug (up to approximately 49 months)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic
state: Illinois
city: Nyack
country: United States
facility: Hematology-Oncology Associates Of Rockland
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Houston
country: United States
facility: The University Of Texas Md Anderson Cancer Center
state: Texas
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Araujo JC, Mathew P, Armstrong AJ, Braud EL, Posadas E, Lonberg M, Gallick GE, Trudel GC, Paliwal P, Agrawal S, Logothetis CJ. Dasatinib combined with docetaxel for castration-resistant prostate cancer: results from a phase 1-2 study. Cancer. 2012 Jan 1;118(1):63-71. doi: 10.1002/cncr.26204. Epub 2011 Jul 25.