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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Sorafenib alone	Sorafenib	Sorafenib: taken daily (oral)
Ascorbic Acid + Sorafenib	Ascorbic Acid + Sorafenib	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)

Primary Outcome Measures

Name	Time	Method
Number of Participants That Experience Serious Adverse Events.	16 weeks +/- 2 weeks	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

Secondary Outcome Measures

Name	Time	Method
Overall Tumor Response Rate	16 weeks +/- 2 weeks	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.
Mean Value Collected Using the Functional Assessment of Cancer Therapy-General (FACT-G) Quality Assessment Instrument	16 weeks +/- 2 weeks	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)
Number of Participants That Are Alive After 15 Weeks of Treatment.	15 weeks+	To evaluate duration of tumor response and progression-free survival