Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer

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