Table 2.
Overview of the clinical trials on natural Nrf2 inhibitors for cancer treatment.
| Compounds | Study design | Intervention/treatment | Tumor types | Phase | Status | Primary endpoint | Clinical trial identifier |
|---|---|---|---|---|---|---|---|
| Apigenin | 17 participants, Non-Randomized, Crossover Assignment, Open label | Chamomile Tea | Health | N/A | Completed | Metabolites in plasma/urine | NCT03526081 |
| Luteolin | 4 participants, Non-Randomized, Parallel Assignment, | Luteolin, nano-luteolin | Tongue Neoplasms Carcinoma |
Early I | N/R | gene expression of Caspase 3 to detect apoptosis | NCT03288298 |
| Wogonin | / | / | / | / | N/R | / | N/A |
| Chrysin | / | / | / | / | N/R | / | N/A |
| Halofuginone | 25 participants | halofuginone hydrobromide | Unspecified Adult Solid Tumor, Protocol Specific | I | Completed | N/R | NCT00027677 |
| 30 participants, Randomized, Parallel Assignment, | halofuginone hydrobromide , placebo |
AIDS-related Kaposi Sarcoma, Recurrent Kaposi Sarcoma | II | Completed | Safety, RR | NCT00064142 | |
| Trigonelline | / | / | / | / | N/R | / | N/A |
| Berberine | 1000 participants, Randomized, Parallel Assignment, | Berberine hydrochloride, placebo | Colorectal Adenomas | II-III | Completed | Incidence rate | NCT03281096 |
| 50 participants, Single Group Assignment, open label | Gefitinib, berberine | Lung Adenocarcinoma EGFR Mutation |
II | N/R | PFS; Safety | NCT03486496 | |
| 18 participants, Randomized, Parallel Assignment | Berberine chloride, laboratory biomarker analysis, placebo administration | Ulcerative Colitis | I | Completed | Safety | NCT02365480 | |
| 524 participants, Randomized, Parallel Assignment |
Berberine, amoxicillin, rabeprazole, clarithromycin, bismuth | Gastric Cancer | IV | Enrolling by invitation | Helicobacter pylori, symptoms effective rate | NCT04697186 | |
| 658 participants, Randomized, Parallel Assignment |
Berberine, amoxicillin, esomeprazole bismuth, etracycline, furazolidone | Gastric Cancer | IV | Completed | Helicobacter pylori, symptoms effective rate | NCT03609892 | |
| 1108 participants, Randomized, Parallel Assignment |
Berberine hydrochloride, placebo | Colorectal Adenoma | II-III | Completed | Recurrence rates | NCT02226185 | |
| 100 participants, Randomized, Parallel Assignment | Berberine hydrochloride | Colorectal Adenomas | II-III | Completed | Measured tumor | NCT03333265 | |
| Brusatol | / | / | / | / | N/R | / | N/A |
| Brucein D | / | / | / | / | N/R | / | N/A |
| Cryptotanshinone | / | / | / | / | N/R | / | N/A |
| Ginsenoside Rd | / | / | / | / | N/R | / | N/A |
| Ascorbic acid | 30 participants, Randomized, Parallel Assignment | Ascorbic acid | Breast Cancer | I-II | N/R | Safety, tolerability and RR | NCT03175341 |
| 21 participants, Single Group Assignment, open label | Ascorbic acid | Bladder Cancer | I-II | Recruiting | Pathological Staging | NCT04046094 | |
| 200 participants, Randomized, Parallel Assignment | Ascorbic acid in combination with mFOLFOX6 | Gastric Cancer | III | N/R | PFS, OS, RR | NCT03015675 | |
| 31 participants, Single Group Assignment, open label | Vitamin C | Prostatic Neoplasms | II | Completed | Biomarkers change (PSA, bALP, NTX, PINP) | NCT01080352 | |
| 15 participants, Single Group Assignment, open label | Gemcitabine with escalating ascorbic acid | Pancreatic Neoplasms | I | Completed | Blood cell counts | NCT01049880 | |
| 97 participants, Randomized, Parallel Assignment | Vitamin C + supportive care | Stage IIIA-B, IV NSCLC Recurrent NSCLC |
I-II | Completed | Safety, tolerability, anti-tumor activity, PFS, OS | NCT02655913 | |
| 5 participants, Non-Randomized, Parallel Assignment | Ascorbic acid in combination with sorafenib | Metastatic Hepatocellular Carcinoma Advanced Liver Cancer |
I-II | Completed | Safety, overall tumor response rate | NCT01754987 | |
| 60 participants, Randomized, Parallel Assignment | Vitamin C, E and Zinc | Skin Neoplasms | N/R | Completed | Oxidative stress biomaker | NCT02248584 | |
| 42 participants, Randomized, Parallel Assignment | Nutritional supplement | Head and Neck Cancer | N/R | Completed | POSAS | NCT03531190 | |
| Triptolide | 30 participants, Single Group Assignment, open label | Procedure: Biopsy; osimertinib, triptolide analog | Advanced lung non-small cell carcinoma | I | Recruiting | MTD, PFS, OS | NCT05166616 |
| 66 participants, Non-Randomized, Parallel Assignment, | Minnelide™Capsules | Gastric, breast, pancreatic, prostate, colorectal cancer, solid tumor, solid carcinoma of stomach, cancer of stomach | I | Recruiting | Safety, anti-tumor activity | NCT03129139 | |
| 55 participants, Single Group Assignment, open label | Minnelide | Adenosquamous carcinoma of the pancreas | II | Recruiting | DCR, PFS, safety, tolerability, OS | NCT04896073 | |
| 19 participants, Single Group Assignment, open label | Minnelide | Pancreatic cancer | II | Completed | DCR, PFS, OS, RR | NCT03117920 |
The list above did not include those studies that were either suspended or terminated prematurely. (N/A, not applicable; N/R, not reported; NSCLC, non-small cell lung cancer; POSAS, The patient and observer scar assessment scale; MTD, Maximum tolerated dose; PFS, Progression-free survival; OS, Overall survival; DCR, Disease control rate; RR, Response rate).