Table 2.
Detailed characteristics of studies with OBD
| Article | Location | Type of treatment | Studied molecules | Escaladed molecules | Phase | Principal objective | Primary endpoint | Statistical design | Secondary endpoints | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OBDa | Clinical response | Immune response | Survival outcome | PK and/or PD | |||||||||
| [14] | Solid | Immunotherapy |
Interleukin 2 13-cis Retinoic Acid |
Interleukin 2 | Phase I | OBD | DLT + IR | Consecutive/sequential cohorts | CR (WHO response criteria) | IR (changes of total T- and T-helper cell counts) | TTP, OS | ||
| [15] | Solid | Immunotherapy | Interleukin 12 Trastuzumab | Interleukin 12 | Phase I | MTD | DLT | 3 + 3 | DLT + IR | CR (not specified) | IR (induction of systemic NK cell-derived cytokines) | ||
| [16] | Melanoma | Immunotherapy | Set of combination immunotherapies | Set of combination immunotherapies | Phase I/II | OBD | DLT + IR | CRM for two binary endpoints | IR (levels of peptide-reactive CD8+ cells) | ||||
| [17] | Melanoma | Immunotherapy |
Recombinant human IL-12 Melan-A and influenza peptides |
Recombinant human IL-12 | Phase I | OBD | Toxicity + IR | Other | CR | IR (cytotoxic lymphocyte response + cutaneous responses) | |||
| [18] | Solid | Metabolic therapy | Pegylated recombinant human arginase 1 | Pegylated recombinant human arginase 1 | Phase I | OBD | DLT + plasma arginine depletion | Modified fibonacci | CR (RECIST criteria) | PFS, OS | PK/PD | ||
| [19] | Melanoma | Metabolic therapy |
High dose paracetamol Carmustine |
High dose paracetamol Carmustine |
Phase I | MTD | DLT | 3 + 3 | Toxicity + effects on GSH levels | CR | PK | ||
| [20] | Solid | Oncolytic Virus therapy | NV1020 | NV1020 | Phase I/II | MTD | DLT | Consecutive/sequential cohorts | DLT + CR | CR (RECIST criteria) | TTP, OS | PK | |
| [21] | Solid | Radiotherapy | Carbon ion | Carbon ion | Phase I/II | OBD | DLT + local control rate | Other | OS, cause specific survival | ||||
| [22] | Solid | Radiotherapy | Carbon ion | Carbon ion | Phase I | MTD | DLT | 3 + 3 | DLT + CR | CR (RECIST criteria) | PFS, OS | ||
| [23] | Solid | Radiotherapy | Carbon ion | Carbon ion | Phase I | OBD | DLT + tumor response at 6 months | Other | Local control | OS | |||
| [24] | Hematologic | Targeted therapy | Acadesine | Acadesine | Phase I/II | MTD | DLT | Modified fibonacci | DLT + CR | CR (IWG response criteria) | PK/PD | ||
| [25] | Hematologic | Targeted therapy |
Venetoclax Ibrutinib |
Venetoclax Ibrutinib |
Phase I | OBD | DLT + ORR at 2 months | CRM for two binary endpoints | CR (Cheson modified criteria) | ||||
| [26] | Solid | Targeted therapy | Angiotensin 1–7 | Angiotensin 1–7 | Phase I/II | OBD/MTD | DLT + response data for white, platelets and red blood cells | 3 + 3 | PK | ||||
| [27] | Solid | Targeted therapy | Emactuzumab | Emactuzumab | Phase I | OBD/MTD | DLT + (PK profile + all response data) | 3 + 3 | CR (RECIST criteria) | Duration of clinically progression-free follow-up | PK/PD | ||
| [28] | Solid | Targeted therapy | Recombinant human thrombopoietin Carboplatin | Recombinant human thrombopoietin | Phase I/II | OBD | Biological response (platelet count response) | Consecutive/sequential cohorts | |||||
| [29] | Solid | Targeted therapy |
NGR-hTNF Oxaliplatin Capecitabine |
NGR-hTNF | Phase I | OBD/MTD | DLT + PK/PD (NGR-hTNF and sTNF receptors 1 and 2) | Consecutive/sequential cohorts | CR (RECIST criteria) | PFS | PK/PD | ||
| [30] | Solid | Targeted therapy |
Eltrombopag Doxorubicin Ifosfamide |
Eltrombopag | Phase I | MTD | DLT | Consecutive/sequential cohorts | Thrombocytopenia + platelet counts | PK/PD | |||
| [31] | Solid | Targeted therapy | NGR-hTNF | NGR-hTNF | Phase I | MTD | DLT | Consecutive/sequential cohorts | DLT + CR | CR (RECIST criteria) | PFS, OS | PK/PD | |
| [32] | Solid | Targeted therapy | Cilengitide | Cilengitide | Phase I | OBD | DLT + biological activity rate (BAR) | Consecutive/sequential cohorts | CR (RECIST criteria) | PK/PD | |||
| [33] | Solid | Targeted therapy |
Celecoxib Erlotinib |
Celecoxib | Phase I | OBD | DLT + urinary PGE-M level | Consecutive/sequential cohorts | CR (RECIST criteria) | ||||
| [34] | Solid | Targeted therapy | WX-554 | WX-554 | Phase I | OBD/MTD | DLT + maximal target inhibition | 3 + 3 | CR (RECIST criteria) | PK/PD | |||
| [35] | Solid | Targeted therapy |
All-trans-retinoic acid Tamoxifen Alpha-interferon 2a |
All-trans-retinoic acid (ATRA) | Phase I | OBD | Biological response | Consecutive/sequential cohorts | PK | ||||
DLT dose limiting toxicity, IR immune response, CR clinical response, OS overall survival, PFS progression-free survival, TTP time to progression, PK pharmacokinetics, PD pharmacodynamics
a Endpoints related to OBD as secondary objective