Table 1.
Ongoing clinical trials targeting and evaluating hypoxia in the tumor microenvironment.
| Clinical Trial | Trial Phase | Drug | Mechanism | Disease | References |
|---|---|---|---|---|---|
| Hypoxia activated prodrug | |||||
| NCT03224182 | III | Apaziquone | Indolequinone | Non-muscle invasive bladder cancer | Clinicaltrials.gov |
| NCT02174549 | I/II | Tirapazamine + transarterial embolization | Aromatic n-oxide | Liver cancer | Clinicaltrials.gov |
|
NCT01880359 NCT02661152 |
III | Nimorazole + chemoradiotherapy | 5-nitroimidazoles, radiosensitizer |
Locally advanced head and neck squamous cell cancer | Clinicaltrials.gov |
| HIF inhibitors | |||||
| NCT03531827 | II | NLG207 + enzalutamide | HIF-1α/topoisomerase I inhibitor + antiandrogen | Metastatic prostate cancer | [158] |
|
NCT02769962 NCT04669002 |
I/II | EP0057 + olaparib | HIF-1α/topoisomerase I inhibitor + PARP inhibitor | Relapsed/refractory small cell lung cancer Ovarian cancer |
Clinicaltrials.gov |
|
NCT03108066 NCT03216499 |
II | PT2385 | HIF-2α inhibitor | Von Hippel-Lindau associated clear cell renal carcinoma Glioblastoma |
Clinicaltrials.gov |
| NCT02974738 | I | Belzutifan (PT2977) |
HIF-2α inhibitor | Advanced solid tumors | Clinicaltrials.gov |
| NCT04195750 | III | Belzutifan (MK-6482) | HIF-2α inhibitor | Advanced renal cell carcinoma | Clinicaltrials.gov |
| Targeting Associated pathways | |||||
|
NCT01101438 NCT01864096 NCT01697566 NCT03685409 |
III | Metformin | Decreases HIF-1α accumulation | Early-stage breast cancer Low risk prostate cancer Chemoprevention study in endometrial and oral cancer |
[149] |
| NCT02614339 | III | Metformin + traditional chemotherapy | Decreases HIF-1α accumulation | Recurrent colorectal cancer | [149] |
| NCT04275713 | II | Metformin + cisplatin | Decreases HIF-1α accumulation | Locally advanced cervical cancer | [179] Clinicaltrials.gov |
| NCT03117920 | II | Minnelide | HSP70, p300 inhibitors | Refractory pancreatic cancer | [149] |
| NCT03450018 | I/II | SLC0111+ gemcitabine | CAIX | Metastatic pancreatic cancer | [180] |
|
NCT04648033 NCT02628080 |
I | Atovaquone + chemoradiotherapy | Antimalarial drug; Hypoxia modifier via inhibition of mitochondrial complex III | Locally advanced non-small cell lung cancer | [180] Clinicaltrials.gov |
| Combination with immunotherapy or anti-angiogenesis therapy | |||||
| NCT03098160 | I | TH-302 + ipilimumab | HAP + anti-CTLA4 Ab | Advanced solid malignancies | [170] |
| NCT01652079 | II | NLG207 + bevacizumab | HIF-1α/topoisomerase I inhibitor + anti-VEGF Ab | Ovarian/peritoneal cancer | [158] |
| NCT03634540 | II | Belzutifan (PT2977) + cabozantinib | HIF-2α + VEGFR2 inhibitors | Advanced clear cell renal carcinoma | Clinicaltrials.gov |
| NCT04895748 | I/Ib | DFF332 + everolimus + spartalizumab | HIF-2α inhibitor + mTOR inhibitor + anti-PD-1 Ab | Relapsed renal cell carcinoma, advanced malignancies with HIF stabilizing mutations | Clinicaltrials.gov |
| NCT04114136 | II | Metformin or rosiglitazone + nivolumab or pembrolizumab | Decreases HIF-1α accumulation | Advanced solid tumor malignancies | Clinicaltrials.gov |
| Assessment of hypoxia | |||||
| NCT03003637 | IB/II | 18F-FDG PET-CT | Pre and post nivolumab +/- ipilimumab | Advanced/recurrent head and neck carcinoma | [171] |
| NCT03373994 | 18F-FDG PET-CT | Evaluate tumor perfusion and hypoxia | Solid tumors | Clinicaltrials.gov | |
| NCT03646747 | Oxygen enhanced MRI measurement | Pre and post radiotherapy | Head and neck cancer | Clinicaltrials.gov | |
| NCT04309552 | FMISO, FLT PET | Compare FMISO, FLT PET vs. molecular biomarkers of hypoxia and cell proliferation | High grade glioma | Clinicaltrials.gov | |
| NCT02095249 | Pimonidazole followed by prostatectomy | Measure tumor hypoxia via immunohistochemical staining | Prostate cancer | Clinicaltrials.gov | |
| NCT04001023 | 18F-EF5 PET-CT and targeted tumor sampling | Identify molecular differences between hypoxic and non-hypoxic tumors | Advanced ovarian cancer | Clinicaltrials.gov | |
| NCT00568490 | Osteopontin, lysyl oxidase, macrophage inhibiting factor and proteomic technology | Identify hypoxic biomarkers in blood and tumors | Head and neck cancer Lung cancer |
Clinicaltrials.gov | |
| NCT03054792 | 18F-FAZA/BOLD PET-MRI | Measure hypoxia between start and completion of treatment | Pediatric sarcomas | Clinicaltrials.gov | |
| Hypoxia assessment + radiotherapy | |||||
| NCT04846309 | I | FMISO PET + radiation | Hypoxic tumors receive higher dose of radiation | Esophageal cancer | Clinicaltrials.gov |
| NCT02352792 | II | FMISO PET + radiation | Hypoxic tumors receive 10% higher dose of radiation | Head and neck squamous cell carcinoma | Clinicaltrials.gov |
HAP: hypoxia activated prodrug; CAIX: carbonic anhydrase IX; FDG: fluorodeoxyglucose; PET: positron emission tomography; FMISO: fluorine-18 fluoromisonidazole; FLT: fluorine-18 fluorothymidine; 18F EF5: fluorine-18 EF5; 18F-FAZA/BOLD: F18-fluoroazomycin arabinoside/blood oxygen level dependent; MRI: magnetic resonance imaging.