Table 1. Patient characteristics.
| Trial phase | Dose escalation phase | Dose expansion phase | |||||
|---|---|---|---|---|---|---|---|
| Patient cohort | 1 | 2 | 3 | Total | GC + guadecitabine | GC | Total |
| Guadecitabine dose | 20 mg/m2, day 1-5 | 20 mg/m2, day 1-5 + G-CSF | 30 mg/m2, day 1-5 + G-CSF | 20 mg/m2, day 1-5 + G-CSF | |||
| n | 4 | 8 | 5 | 17 | 10 | 10 | 20 |
| Age | |||||||
| Median (IQR) | 63 (57.5 to 70) | 56 (52.5 to 65) | 68 (47 to 70) | 59 (54 to 68) | 68 (58 to 75) | 68 (59 to 71) | 68 (59 to 72) |
| Range | 56 to 73 | 44 to 71 | 38 to 76 | 38 to 76 | 51 to 76 | 34 to 74 | 34 to 76 |
| Gender (%) | |||||||
| Male | 2 (50) | 5 (62.5) | 4 (80) | 11 (64.7) | 9 (90) | 10 (100) | 19 (95%) |
| Female | 2 (50) | 3 (37.5) | 1 (20) | 6 (35.3) | 1 (10) | 0 | 1 (5%) |
| ECOG performance status (%) | |||||||
| 0 | 2 (50) | 5 (62.5) | 2 (40) | 9 (52.9) | 7 (70.0) | 6 (60) | 13 (65) |
| 1 | 2 (50) | 3 (37.5) | 3 (60) | 8 (47.1) | 3 (30.0) | 3 (30) | 6 (30) |
| Missing | 0 | 0 | 0 | 0 | 0 | 1 (10) | 1 (5) |
| Primary tumour site (%) | |||||||
| Urinary tract | 4 (100) | 6 (75) | 1 (20) | 11 (41.2) | 10 (100) | 10 (100) | 20 (100) |
| Pleura | 0 | 0 | 2 (40) | 2 (11.8) | 0 | 0 | 0 |
| Ovary | 0 | 0 | 1 (20) | 1 (5.9) | 0 | 0 | 0 |
| Mediastinum* | 0 | 1 (12.5) | 0 | 1 (5.9) | 0 | 0 | 0 |
| Testis | 0 | 0 | 1 (20) | 1 (5.9) | 0 | 0 | 0 |
| Unknown^ | 0 | 1 (12.5) | 0 | 1 (5.9) | |||
| Histopathology (%) | 0 | 0 | |||||
| Adenocarcinoma | 0 | 0 | 1 (20) | 1 (5.9) | 0 | 0 | 0 |
| Carcinoma* | 0 | 1 (12.5) | 1 (20) | 2 (11.8) | 0 | 0 | 0 |
| Mesothelioma | 0 | 0 | 2 (40) | 2 (11.8) | 0 | 0 | 0 |
| Small cell carcinoma | 0 | 0 | 1 (20) | 1 (5.9) | 0 | 0 | 0 |
| Transitional Cell Carcinoma | 3 (75) | 6 (75) | 0 | 9 (53) | 10 (100) | 10 (100) | 20 (100) |
| Clear cell carcinoma | 1 (25) | 0 | 0 | 1 (5.9) | 0 | 0 | 0 |
| Melanoma | 0 | 1 (12.5) | 0 | 1 (5.9) | 0 | 0 | 0 |
| Tumour stage(%) | |||||||
| T2 | - | - | - | - | 8 (80) | 9 (90) | 17 (85) |
| T3 | - | - | - | - | 2 (20) | 1 (10) | 3 (15) |
| Locally advanced | 0 | 1 (12.5) | 2 (40) | 3 (17.7) | 0 | 0 | 0 |
| Metastatic | 4 (100) | 7 (87.5) | 3 (60) | 14 (82.3) | 0 | 0 | 0 |
| Prior surgery(%) | |||||||
| Yes | 4 (100) | 5 (62.5) | 4 (80) | 13 (76.5) | 0 | 0 | 0 |
| No | 0 | 3 (37.5) | 1 (20) | 4 (23.5) | 10 (100) | 10 (100) | 20 (100) |
| Prior radiotherapy(%) | |||||||
| Yes | 0 | 3 (37.5) | 2 (40) | 5 (29.4) | 0 | 0 | 0 |
| No | 4 (100) | 5 (62.5) | 3 (60) | 12 (70.6) | 10 (100) | 10 (100) | 20 (100) |
| Prior systemic therapy(%) | |||||||
| Yes | 2 (50) | 7 (87.5) | 5 (100) | 14 (82.4) | 0 | 0 | 0 |
| No | 2 (50) | 1 (12.5) | 0 | 3 (17.6) | 10 (100) | 10 (100) | 20 (100) |
| Prior intravesical BCG(%) | |||||||
| Yes | 0 | 0 | 0 | 0 | 0 | 1 (100) | 1 (100) |
| No | 4 (100) | 8 (100) | 5 (100) | 17 (100) | 10 (100) | 9 (90) | 19 (95) |
| Haemoglobin(g/L) | |||||||
| Median (IQR) | 125.0 (105.5 to 140.5) | 133.5 (115.0 to 149.0) | 123.0 (109.0 to 130.0) | 130.0 (110.0 to 141.0) | 139.0 (132.0 to 142.0) | 142.5 (136.0 to 149.0) | 140.0 (134.0 to 145.5) |
| Range | 101.0 to 141.0 | 95.0 to 160.0 | 105.0 to 143.0 | 95.0 to 160.0 | 127.0 to 147.0 | 107.0 to 155.0 | 107.0 to 155.0 |
| Albumin(g/L) | |||||||
| Median (IQR) | 32.0 (28.5 to 37.0) | 41.5 (40.0 to 43.5) | 38.0 (33.0 to 40.0) | 39.0 (33.0 to 41.0) | 41.5 (38.0 to 45.0) | 43.0 (40.0 to 44.0) | 43.0 (39.0 to 44.0) |
| Range | 28.0 to 39.0 | 33.0 to 46.0 | 28.0 to 41.0 | 28.0 to 46.0 | 28.0 to 46.0 | 31.0 to 47.0 | 28.0 to 47.0 |
| GFR(mL/min) | |||||||
| Median (IQR) | 94.7 (87.3 to 122.5) | 89.1 (78.0 to 120.9) | 102.0 (75.0 to 118.0) | 97.2 (79.0 to 120.3) | 78.0 (67.0 to 96.0) | 94.0 (81.0 to 107.0) | 88.5 (69.5 to 97.0) |
| Range | 87.3 to 143.0 | 65.0 to 151.0 | 71.0 to 122.0 | 65.0 to 151.0 | 64.0 to 109.0 | 57.0 to 113.0 | 57.0 to 113.0 |
GC, gemcitabine and cisplatin; G-CSF, granulocyte colony stimulating factor; IQR, inter quartile range; ECOG, Eastern Cooperative Oncology Group; BCG, Bacillus Calmette–Guérin; GFR, glomerular filtration rate; *primary mediastinal germ cell carcinoma; ^biopsy proven melanoma lung metastases with no primary site ever identified