Introduction
Patients and methods
Study design
Patients
Assessments
Statistical analysis
Post hoc analysis
Results
Patients
Demographic/characteristic | Phase I (N = 9) | Phase II (N = 38) |
---|---|---|
Age (years) | ||
Median | 73.0 | 71.5 |
Min–max | 62–86 | 50–85 |
Height (cm) | ||
Median | 166.0 | 165.7 |
Min–max | 156.2–174.4 | 153.4–181.0 |
Weight (kg) | ||
Median | 71.2 | 65.7 |
Min–max | 49.2–88.9 | 49.2–93.0 |
ECOG PSa
| ||
Grade 0 | 8 (88.9) | 25 (65.8) |
Grade 1 | 1 (11.1) | 13 (34.2) |
Total Gleason scoreb at initial diagnosisa
| ||
Low, 2–4 | 0 | 0 |
Medium, 5–7 | 0 | 8 (21.1) |
High, 8–10 | 9 (100.0) | 29 (76.3) |
Unknown | 0 | 1 (2.6) |
Clinical tumor stage (T)c at initial diagnosisa
| ||
TX | 1 (11.1) | 1 (2.6) |
T0 | 0 | 0 |
T1 | 0 | 0 |
T2 | 1 (11.1) | 10 (26.3) |
T3 | 6 (66.7) | 16 (42.1) |
T4 | 1 (11.1) | 10 (26.3) |
Unknown | 0 | 1 (2.6) |
Clinical lymph node stage at initial diagnosisa
| ||
NX | 2 (22.2) | 1 (2.6) |
N0 | 3 (33.3) | 14 (36.8) |
N1 | 4 (44.4) | 22 (57.9) |
Unknown | 0 | 1 (2.6) |
Distant metastasis (M)c at initial diagnosisb
| ||
MX | 0 | 1 (2.6) |
M0 | 3 (33.3) | 17 (44.7) |
M1 | 6 (66.7) | 19 (50.0) |
Unknown | 0 | 1 (2.6) |
Number of bone metastases | ||
0 | 3 (33.3) | 8 (21.1) |
1 | 1 (11.1) | 1 (2.6) |
2–4 | 1 (11.1) | 6 (15.8) |
5–9 | 0 | 7 (18.4) |
≥10 | 4 (44.4) | 16 (42.1) |
Anti-androgen withdrawal syndromea
| ||
Yes | 0 | 4 (10.5) |
Stage of prostate cancera,b
| ||
Localized | 1 (11.1) | 6 (15.8) |
Locally advanced | 2 (22.2) | 11 (28.9) |
Metastatic | 6 (66.7) | 19 (50.0) |
Not classifiable | 0 | 2 (5.3) |
PSA at baseline (ng/mL) | ||
Mean (SD) | 634.82 (1403.52) | 174.94 (307.97) |
Median | 21.60 | 65.80 |
Duration of disease at screening (months) | ||
Mean (SD) | 47.36 (22.23) | 63.11 (38.15) |
Median | 39.93 | 52.83 |
Parameter | Category/statistic | Phase II (N = 38) |
---|---|---|
Cancer treatment history, radiation | Yes | 19 (50.0 %) |
Cancer treatment history, procedure | Yes | 6 (15.8 %) |
Quantity of prior hormone therapy linesa
| 3 | 3 (7.9 %) |
4 | 5 (13.2 %) | |
5 | 13 (34.2 %) | |
6 | 11 (28.9 %) | |
≥7 | 6 (15.8 %) | |
Typical prior hormone therapy, other than GnRH analogue | Bicalutamide | 38 (100.0 %) |
Flutamide | 29 (76.3 %) | |
Estramustine | 30 (78.9 %) | |
Docetaxel | 38 (100 %) | |
Number of prior chemotherapy regimens | 1 | 8 (21.1 %) |
2 | 30 (78.9 %) | |
Duration of prior docetaxel (days) | Median | 198 |
Min–max | 1–1012 |
Category and reason | Phase I (N = 9) | Phase II (N = 38) |
---|---|---|
Discontinuation in multiple-dose period (early termination), n (%) | ||
Adverse event | 0 | 5 (13.2) |
Worsening of disease | 1 (11.1) | 5 (13.2) |
Withdrawal by subject | 0 | 2 (5.3) |
Discontinuation in overall study, n (%) | ||
Adverse event | 0 | 8 (21.1) |
Worsening of disease | 5 (55.6) | 18 (47.4) |
Withdrawal by subject | 0 | 2 (5.3) |
Anti-tumor activity
Response
Best overall response | Evaluation by RECIST assessment committee and investigatora (N = 38) |
---|---|
CR, n
| 0 |
PR, n (%) | 2 (5.3) |
Stable disease, n (%) | 16 (42.1) |
PD, n (%) | 16 (42.1) |
Not evaluated | 4 (10.5) |
CR or PR, n (%) (response rate) | 2 (5.3) |
95 % CIb
| 0.6–17.7 % |
90 % CIb
| 0.9–15.7 % |
CR or PR or stable disease, n (%) (disease control rate) | 18 (47.4) |
95 % CIb
| 31.0–64.2 % |
90 % CIb
| 33.3–61.8 % |
PSA
Response | 160 mg/day (N = 38) |
---|---|
Decline from baseline, patients, n (%) | |
≥ 30 % | 15 (39.5) |
95 % CI | 24.0–56.6 % |
≥50 % | 11 (28.9) |
95 % CI | 15.4–45.9 % |
≥90 % | 4 (10.5) |
95 % CI | 2.9–24.8 % |
Safety
MedDRA, version 14.1, preferred term | All adverse events | Adverse events considered to be related to study drug | ||||
---|---|---|---|---|---|---|
Phase I (N = 9) | Phase II (N = 38) | Total (N = 47) | Phase I (N = 9) | Phase II (N = 38) | Total (N = 47) | |
Overall | 9 (100.0) | 36 (94.7) | 45 (95.7) | 7 (77.8) | 24 (63.2) | 31 (66.0) |
Weight decreased | 1 (11.1) | 16 (42.1) | 17 (36.2) | 0 | 5 (13.2) | 5 (10.6) |
Decreased appetite | 3 (33.3) | 10 (26.3) | 13 (27.7) | 2 (22.2) | 4 (10.5) | 6 (12.8) |
Constipation | 2 (22.2) | 10 (26.3) | 12 (25.5) | 1 (11.1) | 6 (15.8) | 7 (14.9) |
Hypertension | 3 (33.3) | 6 (15.8) | 9 (19.1) | 3 (33.3) | 4 (10.5) | 7 (14.9) |
Cancer pain | 1 (11.1) | 8 (21.1) | 9 (19.1) | 0 | 1 (2.6) | 1 (2.1) |
Nausea | 4 (44.4) | 5 (13.2) | 9 (19.1) | 1 (11.1) | 2 (5.3) | 3 (6.4) |
Electrocardiogram QT prolonged | 0 | 6 (15.8) | 6 (12.8) | 0 | 5 (13.2) | 5 (10.6) |
Fatigue | 2 (22.2) | 4 (10.5) | 6 (12.8) | 2 (22.2) | 4 (10.5) | 6 (12.8) |
Nasopharyngitis | 1 (11.1) | 5 (13.2) | 6 (12.8) | 0 | 0 | 0 |
Pyrexia | 1 (11.1) | 4 (10.5) | 5 (10.6) | 1 (11.1) | 0 | 1 (2.1) |
Somnolence | 0 | 5 (13.2) | 5 (10.6) | 0 | 1 (2.6) | 1 (2.1) |
Rash | 0 | 5 (13.2) | 5 (10.6) | 0 | 1 (2.6) | 1 (2.1) |
MedDRA, version 14.1, preferred term | Phase I totala (N = 9) | Phase II 160 mg (N = 38) |
---|---|---|
Overall | 2 (22.2) | 13 (34.2) |
Cancer pain | 1 (11.1) | 2 (5.3) |
Anemia | 0 | 2 (5.3) |
Disseminated intravascular coagulation | 0 | 2 (5.3) |
General physical health deterioration | 0 | 2 (5.3) |
Cellulitis | 0 | 2 (5.3) |
Tumor pain | 0 | 2 (5.3) |
Bladder tamponade | 0 | 2 (5.3) |