drugset / Trial / NCT02969681
Vitamin C Intravenously With Chemotherapy in Advanced Colorectal Cancer
RandomizedParallel-groupOpen-labelTreatment
Summary
Preclinical study has shown that human colorectal cancer cells harboring KRAS or BRAF mutations are selectively killed by high levels of ascorbic acid (AA). High dose of AA aslo impairs tumor growth in Apc/KRASG12D mutant mice. Previous phase Ⅰ studies have found that high dose iv AA is well tolerated in cancer patients.This protocol is a phase Ⅲ study of AA infusions combined with treatment with FOLFOX +/- bevacizumab versus treatment with FOLFOX +/- bevacizumab alone as first-line therapy in patients with recurrent or advanced colorectal cancer.
Timeline
- Start
- 2017-01
- Primary completion
- 2020-12-30
- Completion
- 2020-12-30
Publications
- Background Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, Muley A, Asara JM, Paik J, Elemento O, Chen Z, Pappin DJ, Dow LE, Papadopoulos N, Gross SS, Cantley LC. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015 Dec 11;350(6266):1391-6. doi: 10.1126/science.aaa5004. Epub 2015 Nov 5.
- Background Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller WH Jr. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008 Nov;19(11):1969-74. doi: 10.1093/annonc/mdn377. Epub 2008 Jun 9.
- Background Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol. 2013 Jul;72(1):139-46. doi: 10.1007/s00280-013-2179-9. Epub 2013 May 14.
- Wang F, He MM, Wang ZX, Li S, Jin Y, Ren C, Shi SM, Bi BT, Chen SZ, Lv ZD, Hu JJ, Wang ZQ, Wang FH, Wang DS, Li YH, Xu RH. Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer. BMC Cancer. 2019 May 16;19(1):460. doi: 10.1186/s12885-019-5696-z.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Vitamin C | Other / unclassified | 1.5 g/kg | Intravenous |
| Background | Bevacizumab | Monoclonal antibody | 5 mg/kg | — |
| Background | Leucovorin | Small molecule | 400 mg/m2 | — |
| Background | Oxaliplatin | Small molecule | 85 mg/m2 | — |
| Background | fluorouracil | Small molecule | 2400 mg/m2 | — |