Table 2.
Ongoing, completed and terminated clinical trials with mTOR and metabolic inhibitors in small cell lung carcinoma
| Target | Drug | In combination with | Cancer types | Line | Phase | Status or result | ClinicalTrials.gov identifier | References | |
|---|---|---|---|---|---|---|---|---|---|
| mTOR pathway inhibitors | mTORC1 | RAD001 (everolimus) | Cisplatin, etoposide | Lung cancer | First | I | Completed (feasible everolimus dose: 2.5 mg/kg; best overall response: partial response) | NCT00466466 | [118] |
| mTORC1 | RAD001 (everolimus) | Carboplatin, etoposide | Small cell lung cancer, other advanced solid tumors | First/second | I | Terminated (reason: number of known toxicities observed despite a treatment-naïve population) | NCT00807755 | ||
| mTORC1 | RAD001 (everolimus) | Small cell lung cancer (previously treated) | Second/third | II | Completed (well tolerated, but limited single agent efficacy) | NCT00374140 | [117] | ||
| mTORC1 | Sirolimus | Auranofin | Non-small cell lung cancer or small cell lung cancer (advanced or recurrent) | Second | I/II | Recruiting | NCT01737502 | ||
| mTORC1 | Temsirolimus | Small cell lung cancer (extensive-stage) | Second | II | Completed (no increase in progression-free survival | NCT00028028 | [116] | ||
| mTORC1 | Temsirolimus | Vinorelbine ditartrate | Unresectable or metastatic solid tumors | First/second | I | Completed (no results available) | NCT01155258 | ||
| mTORC1/C2 | Vistusertib | Small cell lung cancer (relapsed, harboring RICTOR Amplification) | Second | II | Terminated (reason: decision of IP support organization) | NCT03106155 | |||
| mTORC1/C2 | Vistusertib | Navitoclax | Small cell lung cancer (relapsed), other solid tumors | First/second | I/II | Active, not recruiting | NCT03366103 | ||
| PI3K | BKM120 | Cisplatin, etoposide | Small cell lung cancer, other advanced solid tumors | First/second | I | Completed (no results available) | NCT02194049 | ||
| Akt | MK-2206 | Non-small cell lung cancer, small cell lung cancer, thymic malignancies | First/second | II | Active, not recruiting | NCT01306045 | |||
| Metabolic inhibitors | Arginase 1 deficiency | ADI-PEG 20 | Small cell lung cancer (relapsed sensitive or refractory) | Second/third | II | Terminated (reason: lack of efficacy in Cohort 2; slow enrollment in Cohort 1) | NCT01266018 | ||
| Arginase 1 deficiency | ADI-PEG 20 | Gemcitabine, docetaxel | Soft tissue sarcoma, osteosarcoma, Ewing's sarcoma, small cell lung cancer | Second | II | Active, not recruiting | NCT03449901 | ||
| Arginase 1 deficiency | Pegzilarginase | Pembrolizumab | Small cell lung cancer (extensive-stage) | Second | I/II | Completed (no results available) | NCT03371979 | ||
| IGF-1R | Figitumumab | Cisplatin/carboplatin, etoposide | Small cell lung cancer (extensive-stage) | Second | II | Terminated (reason: low participants enrollment and the halting of the figitumumab development program) | NCT00977561 | ||
| IGF-1R | Linsitinib | Small cell lung cancer (relapsed) | Second | II | Completed (safe, but no clinical activity in unselected patients) | NCT01533181 | [119] | ||
| TCA-cycle | CPI-613 (6,8-bis(benzylthio)octanoic acid) | Small cell lung cancer (relapsed or refractory) | Second | I | Completed (no efficacy as a single agent) | NCT01931787 | [120] | ||
| AMPK, oxygen consumption | Metformin | Sintilimab | Small cell lung cancer | Second | II | Recruiting | NCT03994744 | ||
| HMG-CoA reductase | Simvastatin | Cisplatin, irinotecan | Small cell lung cancer (extensive-stage) | First | II | Completed (no increase in survival, possible efficacy in heavy smokers) | NCT00452634 | [121] | |
| HMG-CoA reductase | Simvastatin | Cisplatin, irinotecan | Small cell lung cancer (extensive-stage, chemo-naïve patients) | First | II | Recruiting | NCT01441349 | ||
| HMG-CoA reductase | Simvastatin | Irinotecan | Small cell lung cancer (extensive-stage, relapsed) | Second | II | Not Yet Recruiting | NCT04985201 | ||
| HMG-CoA reductase | Simvastatin | Albumin paclitaxel | Small cell lung cancer (extensive-stage, relapsed) | Second | II | Recruiting | NCT04698941 | ||
| HMG-CoA reductase | Pravastatin | Etoposide, cisplatin/carboplatin | Small cell lung cancer | First | II | Completed (safe, but no survival benefit) | NCT00433498 | [122] |
Akt protein kinase B, HMG-CoA 3-hydroxy-3-methyl-glutaryl-coenzyme A, IGF-1R insulin-like growth factor 1 receptor, mTORC1 mammalian target of rapamycin complex 1, mTORC1/2 mammalian target of rapamycin complex 1/2, PI3K phosphatidylinositol 3-kinase, TCA tricarboxylic acid