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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Hepatocellular Cancer
• Intervention / Treatment: Drug: Vitamin C; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fuxiang Zhou, M.D; Phone Number: +86-027-67813155; Email: fuxiang.zhou@whu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430071
      • Recruiting
      • Zhongnan Hopital of Wuhan University
      • Contact: Fuxiang Zhou, M.D; Phone Number: +86-027-67813155; Email: fuxiang.zhou@whu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years to 75 years.

2. 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.

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 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).
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 2.
7. Signed informed consent.

Exclusion Criteria:

1. 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).
2. Pregnant or lactating female patients.
3. Those who have applied excessive dose of vitamin C or (and) metformin in recent 1 month.
4. Patients with glucose-6-phosphate dehydrogenase deficiency.
5. Patients with hydronephrosis.
6. 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.
7. The patients had mental disorders, and the researchers believed that the patients could not fully or fully understand the possible complications in this study.
8. Have a history of immunodeficiency, including: HIV positive, or other acquired or congenital 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Zhongnan Hospital
• Investigators: Study Chair: Fuxiang Zhou, M.D, Wuhan University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: July 20, 2019
• First Submitted That Met QC Criteria: July 24, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Neoplasms; Carcinoma, Hepatocellular; Liver Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Metformin; Ascorbic Acid
• Other Study ID Numbers: ZNCM

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No