Table 1.
Phase I clinical trials of aldoxorubicin
| n | Design | Tumor histology | Doses | Primary endpoint | Results | Reference |
|---|---|---|---|---|---|---|
| 18 | Open label, single-center, single arm | Various relapsed or refractory advanced solid tumors | 230 or 350 mg/m2 IV 30 min infusion on day 1 every 21 days | PKs |
t1/2: 20.1–21.1 h Mean VD: 3.96–4.08 L/m2 Mean Cl: 0.136–0.152 L/h/m2 |
32 |
| 41 | Open label, single-center, single arm | Various relapsed or refractory advanced solid tumors | 20–340 mg/m2 IV 30 min infusion on day 1 every 21 days | MTD DLT |
MTD: 340 mg/m2 (RP2D 260 mg/m2) DLT: myelosuppression (grades 1–3) and mucositis (grades 1–3) |
33 |
| 25 | Open label, single-center, single arm | Various relapsed or refractory advanced solid tumors | 230, 350, or 450 mg/m2 IV 30 min infusion on day 1 every 21 days | MTD DLT |
MTD: 350 mg/m2 DLT: neutropenia (grade 4) and febrile neutropenia (grade 3) |
34 |
| 27 | Open label, single-center, single arm | Previously treated or untreated advanced STS | 250 mg/m2 IV on day 1 with continuous infusion of I–M days 1–14 every 28 days | Efficacy Toxicity | 42% PR, 58% SD, median PFS not reached Toxicities (grades 3–4): neutropenia (78%), anemia (65%), thrombocytopenia (22%), febrile neutropenia (9%), no decrease in LVEF >20% | 35 |
| 10 | Open label, single-center, single arm | Various relapsed or refractory advanced solid tumors | 175, 240, or 320 mg/m2 plus doxorubicin 35 mg/m2 IV both on day 1 every 21 days | MTD DLT |
MTD: 320 mg/m2 aldoxorubicin and 35 mg/m2 doxorubicin No DLT observed |
36 |
| 22 | Open label, multicenter, single arm | Various relapsed or refractory advanced solid tumors | A 170 mg/m2 + G 900 mg/m2; A 250 mg/m2 + G 900 mg/m2; A 200 mg/m2 + G 750 mg/m2 (A on day 1 and G on days 1–8, every 21 days) | RP2D DLT | RP2D: A 200 mg/m2 + G 500 mg/m2 DLT: thrombocytopenia (grades 3–4) Toxicities (grades 3–4): 13 patients with thrombocytopenia, seven patients with neutropenia, eight patients with anemia, no patients with LVEF <50% of normal |
37 |
Abbreviations: A, aldoxorubicin; Cl, clearance rate; DLT, dose-limiting toxicity; G, gemcitabine; I–M, ifosfamide/mesna; IV, intravenous; LVEF, left ventricular ejection fraction; MTD, maximum-tolerated dose; PFS, progression-free survival; PKs, pharmacokinetics; PR, partial response; RP2D, recommended phase II dose; SD, stable disease; STS, soft tissue sarcoma; t1/2, half-life; VD, volume of distribution.