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

Study Overview
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Brief Summary
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This is an open, prospective, single-arm, multi-cohort clinical study to evaluate the efficacy and safety of high-dose vitamin C combined with metformin in the treatment of malignant tumors.

Official Title
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Clinical Research of High Dose Vitamin C Combined With Metformin in the Treatment of Malignant Tumors

Conditions
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Hepatocellular Cancer, Pancreatic Cancer, Gastric Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: Vitamin C
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years to 75 years. Had a disease status that was measurable or evaluable as defined by Response Evaluation Criteria in Solid Tumors (RECIST, version1.1)： Cohort A: patients with advanced hepatocellular carcinoma who had failed previous standard first-line therapy and could not tolerate or reject existing therapies. Cohort B: patients with advanced pancreatic cancer who had previously failed standard first-line therapy, could not tolerate or reject existing therapies. Cohort C: patients with advanced gastric cancer who had failed previous standard second-line or above treatment, who could not tolerate or reject existing therapies. Cohort D: patients with advanced colorectal cancer who had failed previous standard second-line or above treatment, who could not tolerate or reject existing therapies. 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 upper limit of normal(ULN), ALT and AST≤2.5×the ULN (If liver metastases, serum transaminase≤5×the ULN), serum creatine ≤ 1.5 x ULN, creatinine clearance rate > 50ml/min). At least 4 weeks after the last anti-tumor treatment (surgery, chemotherapy, radiotherapy, biotherapy or endocrine therapy) before enrollment. Had a life expectancy of at least 3 months. Had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2. Signed informed consent. Exclusion Criteria: In the past or at the same time with other malignant tumors (already cure period of IB or cervical, lower levels of noninvasive basal cell or squamous cell cancer, obtain complete remission (CR) > 10 years of breast cancer, obtain complete remission (CR) > 10 years of malignant melanoma, obtain complete remission (CR) > 5 years except of other malignant tumors). Pregnant or lactating female patients. Those who have applied excessive dose of vitamin C or (and) metformin in recent 1 month. Patients with glucose-6-phosphate dehydrogenase deficiency. Patients with hydronephrosis. Had a history of clinically significant or uncontrolled heart disease, including but not limited to: (1)Myocardial infarction. (2)Angina.(3)Congestive heart failure above grade 2 of the New York heart association (NYHA).(4)Ventricular arrhythmias requiring continuous treatment.(5)Supraventricular arrhythmias, including uncontrolled atrial fibrillation. The patients had mental disorders, and the researchers believed that the patients could not fully or fully understand the possible complications in this study. Have a history of immunodeficiency, including: HIV positive, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation. Those who cannot tolerate or may be allergic to the drugs used in this study. Participated in clinical trials of other drugs within the past 1 month. Other factors considered unsuitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>Vitamin C combined with metformin | Drug: Vitamin C<br>* Participants will receive intravenous Vitamin C injection (dose: 1.5g/kg, D1-3, every 2 weeks), treatment termination when the disease progress is confirmed.<br>* Other names: Ascorbic acid;Drug: Metformin<br>* Participants will orally take metformin 4g daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival | Defined as time from first dose of treatment to death from any cause, or even radiological detection/or clinical of disease progression. | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Defined as time from first dose of treatment until death. | up to 12 weeks | 
| Objective response rate | Overall Response Rate, as determined by the percentage of patients achieving Partial or Complete response per RECIST 1.1. | up to 12 weeks | 
| Disease control rate | Disease Control Rate: the number of patients with a CR, PR or SD lasting at least 2 months per RECIST 1.1. | up to 12 weeks | 
| Changes of quality of life | Examination of quality of life by EORTC QLQ-C30 questionnaire every 8 weeks. | up to 12 weeks | 
| Number of participants with treatment-related adverse events as assessed by CTCAE v3.0 | The number of grade 1-4 and grade 5 (fatal) NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) events during treatment. All patients will be evaluable for toxicity from the time of their first treatment. | up to 12 weeks |