Table 1.
Ongoing clinical trials with therapies directly or indirectly modulating ROS metabolism.
| Molecule | Mechanism | Phase | Combination (Cancer type) | Clinical Trial ID |
|---|---|---|---|---|
| Inhibiting ROS: | ||||
| Vitamin E, Tocotrienol | Lipid Antioxidant | Phase 2 | Stereotactic Ablative Radiotherapy and Pentoxifylline (Lung cancer) | NCT01871454 |
| Vitamin A (high dose) |
Lipid Antioxidant | Early Phase 1 | Neoadjuvant (Lung cancer) | NCT03870529 |
| N-acetyl cysteine | General antioxidant, to alleviate the side effects of standard therapy | Phase 1,2 | Low dose phase 1, high dose with paclitaxel Phase 2 (solid tumors) | NCT03492047 |
| Phase 2 | Chemotherapy and radiation (head and neck) | NCT03982537 | ||
| Activating ROS: | ||||
| AG-120 (Ivosidenib) or AG881 | Suppression of D-2-HG in IDH1 mutant cancers | Phase 1 | (Low grade glioma) | NCT03343197 |
| Phase 1 | (myeloid cancers) | NCT03564821 | ||
| Phase 1 | (AML) | NCT02074839 | ||
| Phase 1 | (solid tumors) | NCT02073994 | ||
| Phase 1,2 | Azacitidine, Venetoclax (AML) | NCT03471260 | ||
| Phase 3 | Azacitidine (AML) | NCT03173248 | ||
| ARQ761 (β-lapachone) | Nqo1 Substrate, causes oxidoreduction and production of O2•–, depletion of NAD(P)H | Phase 1 | (solid tumors) | NCT01502800 |
| Phase 1 | PARP inhibitor Olaparib (solid tumors) | NCT03575078 | ||
| Phase 1 | Gemcitabine, nab-paclitaxel (PDA) | NCT02514031 | ||
| Ascorbate (High dose ascobic acid) | NADPH and GSH depletion, Increasing H2O2 Levels | Phase 1,2 | (soft tissue sarcomas) | NCT03508726 |
| Phase 1 | Gemcitabine and radiation (PDA) | NCT01852890 | ||
| Phase 2 | nab-paclitaxel with gemcitabine (PDA) | NCT02905578 | ||
| Phase 2 | Gemcitabine and radiation (PDA) | NCT03541486 (XACT-PANC-2) | ||
| Phase 1 | Temozolomide and radiation (GBM) | NCT01752491 | ||
| Phase 2 | Temozolomide and radiation (GBM) | NCT02344355 | ||
| Phase 1 | low dose melphalan + high dose ascorbate acid (Myeloma) | NCT03602235 | ||
| Phase 1,2 | Tyrosine Kinase Inhibitors (Lung cancer) | NCT03799094 | ||
| Phase 2 | Radiotherapy with carboplatin and paclitaxel (Lung cancer) |
NCT02905591 (XACT-LUNG) |
||
| Phase 2 | carboplatin and paclitaxel (Lung cancer) | NCT02420314 | ||
| Phase 2 | (solid tumors) | NCT03146962 | ||
| CB-839 | Glutaminase Inhibitor | Phase 1,2 | Nivolumab (RCC, Lung) | NCT02771626 |
| Phase 2 | Everolimus (RCC) | NCT03163667 | ||
| Phase 2 | Cabozantinib (RCC) | NCT03428217 | ||
| Phase 1,2 | Osimertinib (Lung cancer, EGFR mutation) | NCT03831932 | ||
| Phase 1 | Niraparib (platinum resistant BRCA wild-type ovarian cancer) | NCT03944902 | ||
| Phase 2 | paclitaxel (TNBC) | NCT03057600 | ||
| Phase 1,2 | Panitumumab and irinotecan hydrochloride (CC) | NCT03263429 | ||
| Phase 1,2 | Capecitabine (solid tumors, CC) | NCT02861300 | ||
| Phase 1 | Carfilzomib, and dexamethasone (plasma cell myeloma) | NCT03798678 | ||
| Phase 1 | Single agent, combination with standard chemotherapy (Solid tumors) | NCT02071862 | ||
| Phase 1,2 | CDK4/6 Inhibitor Palbociclib (solid tumors) | NCT03965845 | ||
| Phase 1,2 | Talazoparib (solid tumors) | NCT03875313 | ||
| Phase 2 | (KEAP1, NRF2, STK11/LKB1 mutant solid tumors) | NCT03872427 | ||
AML= acute myeloid leukemia, GBM = glioblastoma multiforme, MM = multiple myeloma, PDA = pancreatic ductal adenocarcinoma, RCC = renal cell carcinoma, TNBC = triple negative breast cancer, KEAP1 = Kelch-like ECH-associated protein 1, NRF2 = Nuclear factor erythroid 2-related factor 2, STK11/LKB1 = Serine/Threonine Kinase 11/Liver Kinase B1.