Phase 2
Completed N=16
Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer
Source: ClinicalTrials.gov NCT00439270 ↗Enrolled (actual)
16
Serious AEs
37.0%
Results posted
Nov 2013
Primary outcomePrimary: Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel — NA mg
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel |
NA | — |
| PRIMARY Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2 |
100 | — |
| SECONDARY Percentage of Participants With a Prostate Specific Antigen (PSA) Response |
64.7 | — |
| SECONDARY Duration of Prostate Specific Antigen (PSA) Response |
9.5 | — |
| SECONDARY Number of Months of Progression-free Survival (PFS) |
11.5 | — |
| SECONDARY Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) |
44.1 | — |
| SECONDARY Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 15; 1; 3; 2; 13 | — |
| SECONDARY Number of Participants by Best On-study Bone Scan Assessment From Baseline |
8; 17; 7; 1; 1 | — |
| SECONDARY Percentage of Participants With Improvement on Bone Scan |
23.5 | — |
| SECONDARY Baseline Scores and Changes in Pain Intensity From Baseline on the Brief Pain Inventory Short Form (BPI-sf) Scores Through Cycle 6 |
1.0; 1.0; -0.8; 0.0; -0.5; -0.0 | — |
| SECONDARY 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 |
3; 17; 8; 45; 7; 13 | — |
| SECONDARY 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 |
2; 7; 33; 6; 12 | — |
| SECONDARY 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 |
173.13; 71.75; 149.79; 277.07; 461.82; 205.43 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Dasatinib and of Docetaxel |
42.70; 21.99; 30.00; 83.91; 164.99; 2226.25 | — |
| SECONDARY Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity (AUC[Inf]) of Docetaxel |
3085.59; 2064.49; 2113.37; 2663.83; 3283.27 | — |
| SECONDARY Number of Participants Meeting the Criteria for On-study Abnormal Results Grade 3-4 of Clinical Laboratory Tests |
0; 0; 0; 1; 0; 0 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT00439270). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.