From: Optimal biological dose: a systematic review in cancer phase I clinical trials
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 | DLTÂ +Â IR | Consecutive/sequential cohorts | Â | CR (WHO response criteria) | IR (changes of total T- and T-helper cell counts) | TTP, OS | Â |
[15] | Solid | Immunotherapy | Interleukin 12 Trastuzumab | Interleukin 12 | Phase I | MTD | DLT | 3Â +Â 3 | DLTÂ +Â IR | CR (not specified) | IR (induction of systemic NK cell-derived cytokines) | Â | Â |
[16] | Melanoma | Immunotherapy | Set of combination immunotherapies | Set of combination immunotherapies | Phase I/II | OBD | DLTÂ +Â IR | CRM for two binary endpoints | Â | Â | IR (levels of peptide-reactive CD8+ cells) | Â | Â |
[17] | Melanoma | Immunotherapy | Recombinant human IL-12 Melan-A and influenza peptides | Recombinant human IL-12 | Phase I | OBD | Toxicity + IR | Other | Â | CR | IR (cytotoxic lymphocyte response + cutaneous responses) | Â | Â |
[18] | Solid | Metabolic therapy | Pegylated recombinant human arginase 1 | Pegylated recombinant human arginase 1 | Phase I | OBD | DLTÂ +Â plasma arginine depletion | Modified fibonacci | Â | CR (RECIST criteria) | Â | PFS, OS | PK/PD |
[19] | Melanoma | Metabolic therapy | High dose paracetamol Carmustine | High dose paracetamol Carmustine | Phase I | MTD | DLT | 3Â +Â 3 | Toxicity + effects on GSH levels | CR | Â | Â | PK |
[20] | Solid | Oncolytic Virus therapy | NV1020 | NV1020 | Phase I/II | MTD | DLT | Consecutive/sequential cohorts | DLTÂ +Â CR | CR (RECIST criteria) | Â | TTP, OS | PK |
[21] | Solid | Radiotherapy | Carbon ion | Carbon ion | Phase I/II | OBD | DLTÂ +Â local control rate | Other | Â | Â | Â | OS, cause specific survival | Â |
[22] | Solid | Radiotherapy | Carbon ion | Carbon ion | Phase I | MTD | DLT | 3Â +Â 3 | DLTÂ +Â CR | CR (RECIST criteria) | Â | PFS, OS | Â |
[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 | DLTÂ +Â CR | CR (IWG response criteria) | Â | Â | 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) | 3Â +Â 3 | Â | CR (RECIST criteria) | Â | 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 | Â | Â | Â | Â | Â |
[29] | Solid | Targeted therapy | NGR-hTNF Oxaliplatin Capecitabine | NGR-hTNF | Phase I | OBD/MTD | DLTÂ +Â PK/PD (NGR-hTNF and sTNF receptors 1 and 2) | Consecutive/sequential cohorts | Â | CR (RECIST criteria) | Â | PFS | PK/PD |
[30] | Solid | Targeted therapy | Eltrombopag Doxorubicin Ifosfamide | Eltrombopag | Phase I | MTD | DLT | Consecutive/sequential cohorts | Thrombocytopenia + platelet counts | Â | Â | Â | PK/PD |
[31] | Solid | Targeted therapy | NGR-hTNF | NGR-hTNF | Phase I | MTD | DLT | Consecutive/sequential cohorts | DLTÂ +Â CR | CR (RECIST criteria) | Â | PFS, OS | PK/PD |
[32] | Solid | Targeted therapy | Cilengitide | Cilengitide | Phase I | OBD | DLTÂ +Â biological activity rate (BAR) | Consecutive/sequential cohorts | Â | CR (RECIST criteria) | Â | Â | PK/PD |
[33] | Solid | Targeted therapy | Celecoxib Erlotinib | Celecoxib | Phase I | OBD | DLTÂ +Â urinary PGE-M level | Consecutive/sequential cohorts | Â | CR (RECIST criteria) | Â | Â | Â |
[34] | Solid | Targeted therapy | WX-554 | WX-554 | Phase I | OBD/MTD | DLTÂ +Â maximal target inhibition | 3Â +Â 3 | Â | CR (RECIST criteria) | Â | Â | 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 | Â | Â | Â | Â | PK |