Adjunctive Intravenous Ascorbic Acid for Advanced Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a two arm RCT evaluating the effect of intravenous vitamin C versus placebo in patients with incurable non-small cell lung cancer. Participants in both arms will be receiving platinum doublet chemotherapy with or without concurrent immunotherapy as standard care. We plan to enroll 90 patients over 5 years.

Official Title
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Adjunctive Intravenous Ascorbic Acid for Advanced Non-Small Cell Lung Cancer: A Double Blind, Placebo Controlled, Phase II Randomized Controlled Trial

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Ascorbic acid
* Other: Normal Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (≥18 years of age) seen at TOHCC with stage IIIB or IV primary non-small cell lung cancer Eligible and scheduled for first line platinum-doublet chemotherapy with or without concurrent immunotherapy Exclusion Criteria: ECOG status greater than 2 Previously received IVC within 6 months prior to randomization Biochemical deficiency in G6PD Estimated Glomerular Filtration Rate (eGFR) less than 45 mL/min Currently taking insulin or warfarin History of severe renal dysfunction or hemochromatosis Previously undergone cytotoxic chemotherapy or immunotherapy within 12 months prior to randomization If pregnant or planning to become pregnant: not a carrier of the gene for G6PD deficiency Currently taking an investigational product or participation in an investigational study within the past 30 days Any reason which, under the discretion of the Principal Investigator or delegate, would preclude the patient from participating

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intravenous Vitamin C<br>1g/kg IVC administered twice weekly for 6 months. | Drug: Ascorbic acid<br>* High dose ascorbic acid delivered intravenously<br>* Other names: Vitamin C;|
| Placebo Comparator: Normal Saline<br>Equivalent volume normal saline administered twice weekly for 6 months. | Other: Normal Saline<br>* 0.9% NaCl solution<br>* Other names: Sodium Chloride Solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life | Participant reported quality of life (QOL) measured using the Functional Assessment of Cancer Therapy - Lung (FACT-L). FACT-L is a validated tool for assessing QOL in patients with lung cancer. FACT scores are normalized to values between 0-100, where 0 is the worst QOL and 100 is the best QOL imaginable. Each chemotherapy cycle is 3 weeks in length. | Baseline, Chemo cycles 1-4, 6 months, 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy-Related Toxicities | Frequency of adverse events (AE) which are commonly experienced by patients undergoing chemotherapy. Measured using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). 31 symptoms were selected by the investigators. | 12 months | 
| Frequency of Discontinuation of Chemotherapy | Patients often discontinue chemotherapy due to side effects. The investigators will monitor the incidence of stopping chemotherapy and compare the number of patients who stop chemotherapy in both arms. | 6 months | 
| Change in General Symptom Burden | Measured using the Edmonton Symptom Assessment Scale, which measures 9 symptoms commonly experienced by cancer patients. Each symptom is rated on a scale of 0-10, where 0 is the best symptom and 10 is the worst symptom. Each chemotherapy cycle is 3 weeks in length. | Baseline, chemo cycles 1-4, 6 months, 12 months | 
| Change in C-Reactive Protein Levels | The investigators will monitor the changes in C-reactive protein (CRP), a common indicator of systemic inflammation. Mean changes in CRP will be compared between arms. Each chemotherapy cycle is 3 weeks in length. | Baseline, chemo cycles 1-4, 6 months, 12 months | 
| Tumour Progression | The investigators will monitor tumour progression using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, which measures the incidence of complete response, partial response, stable disease, and progressive disease during treatments. | 12 months | 
| Survival | The incidence of all cause mortality will be compared between arms. | 24 months | 
| Safety | The investigators will monitor the incidence of all adverse events in both arms to add to the safety profile of IVC in this population. | 6 months | 
| Cytotoxicity | The investigators will assess the ability of IVC to bring serum ascorbate levels to at least 15mM, which is the hypothesized level at which cytotoxic effects may occur. Levels 15mM or above will be considered adequate. | 12 months |