Vitamin C Colorectal Cancer
Vitamin C Colorectal Cancer
Brief 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Colorectal Neoplasms | Drug: ascorbic acid Drug: Chemotherapy | Phase 3 |
Detailed Description:
Linus Pauling and Dr Ewan Cameron have published two retrospective studies about using high dose vitamin C to treat cancer patients forty years ago. Their studies have shown that high dose vitamin C usage could significantly prolong overall survival of patients with advanced cancer. Recently, 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 impairs tumor growth in Apc/KRASG12D mutant mice. Previous phaseⅠ clinical trials have found that high dose (1.5g/kg or 90g/m2) iv AA is well tolerated in cancer patients. This protocol is a phase Ⅲ, study of ascorbic acid (AA) infusions combined with treatment with FOLOX +/- bevacizumab versus treatment with FOLFOX +/- bevacizumab alone as first-line therapy in patients with recurrent or advanced colorectal cancer.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 428 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase Ⅲ Study of IV Ascorbic Acid in Combination With FOLFOX+/- Bevacizumab vs Treatment With FOLFOX+/- Bevacizumab Alone as First-line Therapy for Advanced Colorectal Cancer |
| Study Start Date : | January 2017 |
| Estimated Primary Completion Date : | December 2019 |
| Estimated Study Completion Date : | December 2020 |
Resource links provided by the National Library of Medicine 
| Arm | Intervention/treatment |
|---|---|
| Experimental: Ascorbic Acid with chemotherapy group Ascorbic Acid with mFOLFOX6 with or without bevacizumab Ascorbic Acid (1.5g/kg/day, D1-3) every 2 weeks mFOLFOX6:
with or without bevacizumab 5mg/kg, every 2 weeks | Drug: ascorbic acid 1.5g/kg/day, D1-3, every 2 weeks Other Name: Vitamin C Drug: Chemotherapy
with or without bevacizumab 5mg/kg, every 2 weeks Other Name: mFOLFOX6+/- bevacizumab |
| Active Comparator: Chemotherapy group mFOLFOX6:
with or without bevacizumab 5mg/kg, every 2 weeks | Drug: Chemotherapy
with or without bevacizumab 5mg/kg, every 2 weeks Other Name: mFOLFOX6+/- bevacizumab |
Primary Outcome Measures :
- Progression Free Survival [ Time Frame: up to 5 years ]
Time-to-event outcome measure (initial disease progression) measured in days from cycle 1 day 1 to day of first progression as defined by RECIST1.1 criteria from NCI
Secondary Outcome Measures :
- Overall Survival [ Time Frame: up to 5 years ]
Time to event outcome measure (death), measured in days from cycle 1 day 1
- Response Rate [ Time Frame: up to 5 years ]
To utilize CT or PET/CT scans to assess overall tumor response rate (complete and partial response) and evaluate disease progression in subjects with advanced or recurrent RAS mutant colorectal cancer treated with the combination of ascorbic acid and FOLOX/FORFIRI +/- bevacizumab versus treatment with FOLFOX/FORFIRI +/- bevacizumab alone
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Age≥18 years, ≤75 years; Histologically proven metastatic adenocarcinoma of colorectal cancer (stage Ⅳ disease), unresectable metastatic disease; measurable disease; G6PD status > lower limit of normal; Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1; Life expectancy of at least 12 weeks; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3; Laboratory at baseline evaluation for inclusion in the study: creatinine ≤1.5X upper limit [if the creatinine is elevated, but ≤1.5X the ULN, a 24 hour creatinine clearance will be obtained, Creatinine clearance > 50 mL/min (calculated according to Cockroft and Gault)]; Transaminase (AST/ALT) ≤2.5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal without liver metastasis; Transaminase (AST/ALT) ≤5X upper limit of normal and bilirubin levels ≤1.5X upper limit of normal with liver metastasis; Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study; Written informed consent
Exclusion Criteria:
Prior treatment for metastatic disease (adjuvant therapy with fluoropyrimidines +/-oxaliplatin based regimens allowed if stopped 12 months prior to registration on study); Surgery (excluding diagnostic biopsy) or irradiation within 3 weeks prior to study entry; Administration of any investigational drug or agent/procedure, i.e. participation in another trial within 4 weeks before beginning treatment; Concurrent chronic systemic immune therapy, chemotherapy, radiation therapy (palliative radiation therapy allowed) or hormone therapy not indicated in the study protocol; Brain metastasis (known or suspected); Pregnant or lactating women; Other uncontrolled concomitant illness, including serious uncontrolled intercurrent infection; Known allergy or any other adverse reaction to any of the drugs or to any related compound; Previous (within 5 years) or concurrent malignancies at other sites with the exception of surgically cured or adequately treated carcinoma in-situ of the cervix and basal cell carcinoma of the skin; Patients who are on strong inducers of CYP3A4 which include but are not limited to: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Dexamethasone, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort; Medical, social or psychological condition which, in the opinion of the investigator, would not permit the patient to complete the study or sign meaningful informed consent; Organ allograft requiring immunosuppressive therapy; Patients with HIV infection
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02969681
| China, Guangdong | |
| Medical Oncology,Sun Yat-sen University Cancer Center | Recruiting |
| Guangzhou, Guangdong, China, 510060 | |
| Contact: Feng Wang, M.D,Ph.D 86-18620880867 wangfeng@sysucc.org.cn | |
| Principal Investigator: Ruihua Xu, M.D,Ph.D | |
| Sub-Investigator: Feng Wang, M.D,Ph.D | |
Sun Yat-sen University
| Principal Investigator: | Rui-hua Xu, MD.,PhD. | Sun Yat-sen University |
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.
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.
| Responsible Party: | Ruihua Xu, Clinical Professor, Sun Yat-sen University |
| ClinicalTrials.gov Identifier: | NCT02969681 |
| Other Study ID Numbers: | VitC001 |
| First Posted: | November 21, 2016 Key Record Dates |
| Last Update Posted: | February 27, 2019 |
| Last Verified: | February 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
Additional relevant MeSH terms:
| Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases Gastrointestinal Diseases Colonic Diseases | Intestinal Diseases Rectal Diseases Ascorbic Acid Physiological Effects of Drugs Vitamins Micronutrients Antioxidants Molecular Mechanisms of Pharmacological Action Protective Agents |
Source: https://clinicaltrials.gov/ct2/show/NCT02969681
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