Intravenous Ascorbic Acid Supplementation in Neoadjuvant Chemotherapy for Breast Cancer

Study Overview
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Brief Summary
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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.

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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Ascorbic Acid
* Drug: Placebos


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin C Supplement<br>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<br>* 1,5 g ascorbic acid dissolved in 100 ml sterile water, and 0,75 g ascorbic acid dissolved in 100 ml sterile water.<br>* Other names: Chemotherapy;|
| Active Comparator: Placebo<br>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<br>* 100 ml normal saline 0.9%<br>* Other names: Saline 0.9%;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, ascorbic acid, vitamin C, vitamin supplementation, quality of life