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

• Sponsor: Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01754987
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 40
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Metastatic Hepatocellular Carcinoma; Advanced Liver Cancer	Drug: Ascorbic Acid + Sorafenib; Drug: Sorafenib	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Intravenous Ascorbic Acid in Treatment of Metastatic Hepatocellular Carcinoma
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Jan 1, 2016
• Actual Study Completion Date: Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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)	Drug: Ascorbic Acid + Sorafenib; Other Names: Vitamin C Ascorbate
Other: Sorafenib alone Sorafenib: taken daily (oral)	Drug: Sorafenib; Other Names: Nexavar

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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)

3. Number of Participants That Are Alive After 15 Weeks of Treatment. [15 weeks+]

   To evaluate duration of tumor response and progression-free survival

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Thomas Jefferson University

Investigators

• Principal Investigator: Daniel A Monti, MD, MBA, Thomas Jefferson University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794. doi: 10.1371/journal.pone.0029794. Epub 2012 Jan 17.

• Responsible Party: Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT01754987
• Other Study ID Numbers: 12D.424
• First Posted: Dec 21, 2012
• Last Update Posted: Aug 23, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Thomas Jefferson University: Vitamins; Malignant Tumor, Tumour; Integrative Medicine; Complementary Medicine; Alternative Medicine Antioxidants; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Protective Agents; Physiological Effects of Drugs; Micronutrients; Growth Substances; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Therapeutic Uses; Radiation-Sensitizing Agents; Liver Cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Ascorbic Acid; Sorafenib

Study Results

Participant Flow

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib
Period Title: Overall Study
STARTED	5	0
COMPLETED	5	0
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone	Total
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib	Total of all reporting groups
Overall Participants	5	0	5
Age (Count of Participants)
<=18 years	0 0%	0 NaN
Between 18 and 65 years	3 60%	3 Infinity
>=65 years	2 40%	2 Infinity
Sex: Female, Male (Count of Participants)
Female	2 40%	2 Infinity
Male	3 60%	3 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN
Not Hispanic or Latino	5 100%	5 Infinity
Unknown or Not Reported	0 0%	0 NaN
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN
Asian	0 0%	0 NaN
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN
Black or African American	1 20%	1 Infinity
White	4 80%	4 Infinity
More than one race	0 0%	0 NaN
Unknown or Not Reported	0 0%	0 NaN
Region of Enrollment (participants) [Number]
United States	5 100%	5 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Participants That Experience Serious Adverse Events.
Description	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
Time Frame	16 weeks +/- 2 weeks

Outcome Measure Data

Analysis Population Description

The trial was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib
Measure Participants	0	0

2. Secondary Outcome

Title	Overall Tumor Response Rate
Description	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.
Time Frame	16 weeks +/- 2 weeks

Outcome Measure Data

Analysis Population Description

The trial was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib
Measure Participants	0	0

3. Secondary Outcome

Title	Mean Value Collected Using the Functional Assessment of Cancer Therapy-General (FACT-G) Quality Assessment Instrument
Description	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)
Time Frame	16 weeks +/- 2 weeks

Outcome Measure Data

Analysis Population Description

The trial was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib
Measure Participants	0	0

4. Secondary Outcome

Title	Number of Participants That Are Alive After 15 Weeks of Treatment.
Description	To evaluate duration of tumor response and progression-free survival
Time Frame	15 weeks+

Outcome Measure Data

Analysis Population Description

The trial was closed early due to lack of accrual. The data were not collected or analyzed.

Arm/Group Title	Ascorbic Acid + Sorafenib	Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib	Sorafenib: taken daily (oral) Sorafenib
Measure Participants	0	0

Adverse Events

Arm/Group Title	Ascorbic Acid + Sorafenib		Sorafenib Alone
Arm/Group Description	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) Ascorbic Acid + Sorafenib		Sorafenib: taken daily (oral) Sorafenib
All Cause Mortality
	Ascorbic Acid + Sorafenib		Sorafenib Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ascorbic Acid + Sorafenib		Sorafenib Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		0/0 (NaN)
General disorders
Dehydration	1/5 (20%)	1	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Ascorbic Acid + Sorafenib		Sorafenib Alone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/0 (NaN)
Blood and lymphatic system disorders
Elevated Creatinine	2/5 (40%)	2	0/0 (NaN)	0
Nosebleed	1/5 (20%)	1	0/0 (NaN)	0
Low Platelet count	2/5 (40%)	2	0/0 (NaN)	0
Infections and infestations
Thrush	1/5 (20%)	1	0/0 (NaN)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.