A Study of Vitamin C in the Treatment of Liver Cancer to Determine if it is Safe and Effective

Study Overview
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Brief Summary
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This protocol is a phase I/II, study of ascorbic acid (AA) infusions combined with treatment with sorafenib versus treatment with sorafenib alone in subjects with metastatic hepatocellular carcinoma. The phase I aspect will assess the safety and efficacy of the concurrent treatments and the phase II aspect will utilize CT (computer-tomography) scans to assess overall tumor response rate and evaluate disease progression

Detailed Description
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Intravenous Ascorbic Acid (Vitamin C) is a widely used alternative cancer treatment. This trial will study an intravenous Vitamin C treatment for persons with liver cancer that has spread, who are also receiving Sorafenib (a standard cancer drug), to see whether the combination of Vitamin C and Sorafenib is safe and well tolerated. Phase I will involve 6 persons who will receive the Vitamin C for 8 weeks to more specifically assess the safety of getting Vitamin C in combination with Sorafenib. Phase II will be randomized to receive either Vitamin C plus Sorafenib or Sorafenib alone for 16 weeks. If Vitamin C has a beneficial effect on tumour cells, patients may experience a regression of tumor or tumor markers. Additional benefits include scans at no charge to the patient.

Official Title
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Phase I/II Study of Intravenous Ascorbic Acid in Treatment of Metastatic Hepatocellular Carcinoma

Conditions
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Metastatic Hepatocellular Carcinoma, Advanced Liver Cancer

Intervention / Treatment
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* Drug: Ascorbic Acid + Sorafenib
* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years Metastatic hepatocellular carcinoma G6PD (glucose-6-phosphate dehydrogenase) status > lower limit of normal Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2. 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); transaminase (AST/ALT) ≤2.0X upper limit of normal; bilirubin levels ≥ 2 mg/dL; ANC ≥1,500/mm3; Hemoglobin > 8g/dL; platelet ≥ 100,000/mm3 Women of childbearing potential will confirm a negative pregnancy test and must practice effective contraception during the study. Willing and able to provide informed consent and participate in the study procedures. Exclusion Criteria: Patients with evidence of a significant current psychiatric disorder that would prevent completion of the study as determined by the PI will not be allowed to participate. Co-morbid medical condition that would affect survival or tolerance as determined by the PI. This includes patients who have not fully recovered from toxicities associated with prior therapy. It also includes subjects who, as determined by the PI, are at risk of experiencing fluid overload (i.e., congestive heart failure). Patients who currently abuse alcohol or drugs. Patients with known glomerular filtration rate of <60ml/min or with nephrotic range proteinuria. Pregnant or lactating women Enrollment in active clinical trial/ experimental therapy or IND study within the prior 30 days. Contraindication for CT or PET/CT as per the PI.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ascorbic Acid + Sorafenib<br>Drug: Vitamin C Other Names: Ascorbic Acid, Ascorbate Dosage: Vitamin C : 100 grams (infusion) Phase I: 3x a week for 8 weeks Phase II: 3x a week for 16 weeks Sorafenib: taken daily (oral) | Drug: Ascorbic Acid + Sorafenib<br> <br> * Other names: Ascorbate;|
| Other: Sorafenib alone<br>Sorafenib: taken daily (oral) | Drug: Sorafenib<br> <br> * Other names: Nexavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants That Experience Serious Adverse Events. | The primary aim is to assess whether or not (IV) Ascorbic Acid (AA) with sorafenib therapy is relatively safe and well-tolerated according to Common Terminology Criteria for Adverse Events (CTCAE)v4.0 | 16 weeks +/- 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Tumor Response Rate | To utilize CT or PET/CT scans to assess overall tumor response rate (complete) in subjects with advanced metastatic hepatocellular cancer treated with the combination of ascorbic acid and sorafenib versus sorafenib alone. | 16 weeks +/- 2 weeks | 
| Mean Value Collected Using the Functional Assessment of Cancer Therapy-General (FACT-G) Quality Assessment Instrument | To evaluate quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) quality assessment instrument. The FACT-G questionnaire will be used to assess quality-of-life longitudinally. Quality-of-life scores obtained from the FACT-G will be summarized at multiple time points. Five-point scale from 0 (not at all) to 4 (very much) | 16 weeks +/- 2 weeks | 
| Number of Participants That Are Alive After 15 Weeks of Treatment. | To evaluate duration of tumor response and progression-free survival | 15 weeks+ | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Micronutrients, Vitamins, Malignant Tumor, Tumour, Integrative Medicine, Complementary Medicine, Alternative Medicine Antioxidants, Molecular Mechanisms of Pharmacological Action, Pharmacologic Actions, Protective Agents, Physiological Effects of Drugs, Growth Substances, Antineoplastic Agents, Phytogenic, Antineoplastic Agents, Therapeutic Uses, Radiation-Sensitizing Agents, Liver Cancer