Intravenous Ascorbic Acid Supplementation in Neoadjuvant Chemotherapy for Breast Cancer

Phase I/II Randomized Study to Evaluate the Role of Intravenous Ascorbic Acid Supplementation to Conventional Neoadjuvant Chemotherapy in Women With Breast Cancer

Forty years ago clinical studies conducted by Ewan Cameron and Linus Pauling suggested that intravenous (IV) and oral ascorbic acid (AA) may diminish symptoms and could improve survival in terminal cancer patients. Previous phase I and II clinical trials have found that high dose (1.5g/kg ) iv AA is well tolerated in cancer patients. This is a phase I/II, randomized study of parenteral administration of Ascorbic Acid (AA) as a supplement to the conventional neo-adjuvant chemotherapy in women with breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ascorbic Acid; Drug: Placebos

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Romania
  • Sibiu, Romania, 550245
    • Academic Emergency County Hospital Sibiu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2;
• Diagnosed high-risk breast cancers (tumours ≥ 2cm and/or locally advanced breast tumors) and scheduled to receive neoadjuvant chemotherapy;
• Agree to avoid any additional supplemental ascorbic acid throughout the study;
• Normal glucose-6- phosphate dehydrogenase (G6PD) activity;
• Normal renal function (serum creatinine ≤ 1.2 mg/dl) and normal liver function;
• No evidence of urolithiasis;
• No evidence of chronic hemodialysis, iron overload (serum ferritin 500 ng/ml);
• Not pregnant or lactating women

Exclusion Criteria:

• Important psychosomatic diseases or known gastrointestinal disorders (ulcer, gastritis, colitis, ileitis);
• Current smoking and/or alcohol consumption ≥ 3UI per day;
• Current use of the following drugs:

Aspirin (exceeding 325 mg/day) Acetaminophen (exceeding 2 g/day) Glutathione Vitamin D (important doses)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin C Supplement; Ascorbic Acid (AA) with neoadjuvant chemotherapy. Participants received an initial loading dose of 1,5 g Ascorbic Acid (i.v in 100 ml sterile water) on Day 1 followed by 0,75g Ascorbic Acid (i.v in 100 ml sterile water) on Day 2-4 at each chemotherapy cycle and concomitant neoadjuvant chemotherapy regimens administered at the choice of treating physician. Ascorbic Acid is administered intravenously before neoadjuvant therapy in D1	Drug: Ascorbic Acid; 1,5 g ascorbic acid dissolved in 100 ml sterile water, and 0,75 g ascorbic acid dissolved in 100 ml sterile water.; Other Names: Chemotherapy; Vitamin C
Active Comparator: Placebo; Placebos (normal saline (0.9%) with neoadjuvant chemotherapy. 100 ml normal saline 0.9% (placebo) will be administered (i.v) by the same scheme as Ascorbic Acid on Day 1 and respectively Day 2-4 at each chemotherapy cycle. Concomitant neoadjuvant chemotherapy regimens administered at the choice of treating physician.	Drug: Placebos; 100 ml normal saline 0.9%; Other Names: Normal Saline; Saline 0.9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Adverse Events as a Measure of Safety and Tolerability	Assessments are made through analysis of reported incidence of treatment-emergent Adverse Events. Toxicities (AEs) in both groups will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03	during the six months of neoadjuvant chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life	The symptom checklist and the symptom related measures as defined by European Organization for Research and Treatment of Cancer (Questionnaire C30 and BR23) will be compared between arms using frequency tables	At baseline and each 28 days during the six months of neoadjuvant chemotherapy
Therapeutic efficacy	Therapeutic efficacy assessed by Pathological response. Percentage of Participants Achieving Complete Response (CR) According to the Residual Cancer Burden score.	Approximately 6 months
Objective Response Rate	Objective Response Rate using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Guidelines	every 8 weeks, up to 6 months
Effect of AA supplementation on serum inflammatory cytokine	Assessment of laboratory parameters including interleukin (IL)-6 and vascular endothelial growth factor (VEGF).	At baseline and every 8 weeks during the six months of neoadjuvant chemotherapy

Collaborators and Investigators

• Sponsor: Academic Emergency County Hospital Sibiu
• Collaborators: CHU-UCL Namur (site Mont-Godinne), Belgium
• Investigators: Study Director: Florin Grosu, MD,PhD, Academic Emergency County Hospital Sibiu

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2018
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): October 1, 2019

Study Registration Dates

• First Submitted: April 29, 2017
• First Submitted That Met QC Criteria: June 2, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): June 27, 2018
• Last Update Submitted That Met QC Criteria: June 25, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: breast cancer; quality of life; ascorbic acid; vitamin C; vitamin supplementation
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Ascorbic Acid
• Other Study ID Numbers: 6222/22.03.2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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