Table 4. Examples of Phase 0 (Ph0) studies testing MTA in Oncology.
| Family of MTA | MTA | Mechanism of action | Endpoints of the study | Subject dose | Fulfils Ph0 criteria | Reference |
|---|---|---|---|---|---|---|
| Cytotoxic agent radiolabelled with positron emitting radioisotopes |
carbon-11 radiolabelled N-[2-(dimethylamino) ethyl]acridine-4-carboxamide (DACA) |
11C-labelled topoisomerase I/II inhibitor | To evaluate plasma PD effects of drugs using data obtained during PET studies with radiolabelled anti-cancer agents. | DACA at 1/1000th of Ph1, as part of Ph0 micro-dosing study | Yes | [43] |
| Multi-tyrosine kinase inhibitor | imatinib | BCR-ABL and c-KIT inhibitor |
To investigate the potential use of MS for studying pharmacology aspects of imatinib. | Imatinib 400 mg/d plus 13.6 kBq of 14C-imatinib |
Yes | [44] |
| PARP inhibitor |
ABT-888 (veliparib) |
Poly (ADP-ribose) polymerase inhibitor | Proof-of-mechanism of action. To evaluate PARP levels after dosing (PD effect). |
Starting dose 1/50th of NOAEL of sensitive specie | Yes | [7] |
| Transcription factor inhibitor | STAT3 decoy oligonucleotide | STAT3 transcription factor gene inhibition | Proof-of-mechanism of action. To demonstrate inhibition of STAT3 target genes (Bcl, Cyclin D). |
Single intra-tumoral injection of several doses: 250 mg/250uL vs 500 mg/500 uL vs 1000 mg/1000 uL |
Yes | [8] |
Abbreviations: MTA (Molecularly Targeted Agents); PD (PharmacoDynamic); MS (Mass Spectrometry); PARP (Poly [ADP-ribose] polymerase).