High Dose Vitamin C Combined With Metformin in the Treatment of Malignant Tumors

Inclusion Criteria:

1. 18 years to 75 years.
2. Had a disease status that was measurable or evaluable as defined by ResponseEvaluation Criteria in Solid Tumors (RECIST, version1.1)： Cohort A: patients withadvanced hepatocellular carcinoma who had failed previous standard first-line therapyand could not tolerate or reject existing therapies. Cohort B: patients with advanced pancreatic cancer who had previously failed standardfirst-line therapy, could not tolerate or reject existing therapies. Cohort C: patients with advanced gastric cancer who had failed previous standardsecond-line or above treatment, who could not tolerate or reject existing therapies. Cohort D: patients with advanced colorectal cancer who had failed previous standardsecond-line or above treatment, who could not tolerate or reject existing therapies.
3. Adequate hepatic, renal, heart, and hematologic functions (hemoglobin ≥80g/L,platelets ≥ 80×10^9/L, neutrophils ≥ 1.5×10^9/L, total bilirubin within 1.5×the upperlimit of normal(ULN), ALT and AST≤2.5×the ULN (If liver metastases, serumtransaminase≤5×the ULN), serum creatine ≤ 1.5 x ULN, creatinine clearance rate > 50ml/min).
4. At least 4 weeks after the last anti-tumor treatment (surgery, chemotherapy,radiotherapy, biotherapy or endocrine therapy) before enrollment.
5. Had a life expectancy of at least 3 months.
6. Had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or
8. Signed informed consent.

Exclusion Criteria:

1. In the past or at the same time with other malignant tumors (already cure period of IBor cervical, lower levels of noninvasive basal cell or squamous cell cancer, obtaincomplete remission (CR) > 10 years of breast cancer, obtain complete remission (CR) > 10 years of malignant melanoma, obtain complete remission (CR) > 5 years except ofother malignant tumors).
2. Pregnant or lactating female patients.
3. Those who have applied excessive dose of vitamin C or (and) metformin in recent 1month.
4. Patients with glucose-6-phosphate dehydrogenase deficiency.
5. Patients with hydronephrosis.
6. Had a history of clinically significant or uncontrolled heart disease, including butnot limited to: (1)Myocardial infarction. (2)Angina.(3)Congestive heart failure abovegrade 2 of the New York heart association (NYHA).(4)Ventricular arrhythmias requiringcontinuous treatment.(5)Supraventricular arrhythmias, including uncontrolled atrialfibrillation.
7. The patients had mental disorders, and the researchers believed that the patientscould not fully or fully understand the possible complications in this study.
8. Have a history of immunodeficiency, including: HIV positive, or other acquired orcongenital immunodeficiency diseases, or a history of organ transplantation.
9. Those who cannot tolerate or may be allergic to the drugs used in this study.
10. Participated in clinical trials of other drugs within the past 1 month.
11. Other factors considered unsuitable for the study.