Vitamin C for Lung Cancer

(AIVAA Trial)

Overseen By Mark Legacy, BSc, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: The Canadian College of Naturopathic Medicine

Must not be taking: Insulin, Warfarin, Investigational products

Disqualifiers: ECOG > 2, G6PD deficiency, Renal dysfunction, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether high-dose vitamin C, administered through an IV, can aid in treating advanced non-small cell lung cancer. It is a two-arm study: some participants receive vitamin C, while others receive a placebo, alongside their regular chemotherapy and possibly immunotherapy. The researchers aim to determine if vitamin C can improve outcomes for those not curable with current treatments. The trial seeks participants with stage IIIB or IV non-small cell lung cancer who are about to begin platinum-doublet chemotherapy. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking insulin or warfarin to participate. If you are on these medications, you would need to discontinue them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that administering vitamin C through an IV is safe for cancer patients. Studies have found that even at high doses, it doesn't cause major side effects, and patients tolerate these treatments well. Early research on various types of cancer confirms the safety of high-dose IV vitamin C. When combined with other cancer treatments, it doesn't appear to cause additional harm. For most people, IV vitamin C is generally considered safe. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Unlike standard treatments for lung cancer, such as chemotherapy and targeted therapies, this innovative approach uses intravenous Vitamin C. Researchers are excited about this treatment because Vitamin C, or ascorbic acid, is thought to possess powerful antioxidant properties that may specifically target and kill cancer cells without harming healthy cells. Moreover, the delivery method—administering a high dose directly into the bloodstream—ensures that much larger amounts reach the tumor compared to oral ingestion, potentially enhancing its effectiveness. This novel mechanism of action offers hope for a treatment that could be both effective and less toxic than conventional options.

What evidence suggests that intravenous vitamin C could be an effective treatment for lung cancer?

In this trial, participants will receive either high-dose intravenous vitamin C (IVC) or a placebo comparator. Research suggests that high-dose IVC might be a promising cancer treatment. It seems to specifically target cancer cells, causing them to die and halting their growth. This occurs through several mechanisms, such as creating a harmful environment for tumor cells and enhancing the immune system's ability to fight cancer. Some studies have found that while IVC doesn’t significantly change how long patients remain cancer-free, it does slow cancer cell growth in lab tests. Overall, increasing evidence suggests that high-dose IVC may help in fighting lung cancer, but more research is needed to fully understand its benefits. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced non-small cell lung cancer, who are about to start their first round of platinum-doublet chemotherapy, with or without immunotherapy. It's not suitable for those who don't meet these specific conditions.

Inclusion Criteria

I am an adult with stage IIIB or IV non-small cell lung cancer.

I am scheduled for my first chemotherapy with platinum drugs, possibly with immunotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous vitamin C or placebo twice weekly for 6 months alongside standard chemotherapy

6 months

Twice weekly visits

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

6 months

Long-term Follow-up

Participants are monitored for survival and long-term outcomes

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbic acid

Trial Overview

The study compares the effects of high-dose vitamin C given through the vein to a placebo in patients receiving standard chemotherapy treatments. This randomized controlled trial aims to enroll 90 participants and will last five years.

How Is the Trial Designed?

Group I: Intravenous Vitamin C Experimental Treatment 1 Intervention

1g/kg IVC administered twice weekly for 6 months.

Group II: Normal Saline Placebo Group 1 Intervention

Equivalent volume normal saline administered twice weekly for 6 months.

Who Is Running the Clinical Trial?

The Canadian College of Naturopathic Medicine

Lead Sponsor

Trials

23

Recruited

2,600+

Ottawa Hospital Research Institiute

Collaborator

Trials

1

Recruited

90+

Published Research Related to This Trial

Ascorbic acid (AA) and its derivative 6-chloro-6-deoxy ascorbic acid (6-Cl-AA) were found to inhibit the growth of specific cancer cell lines, including HeLa and SK-BR-3 cells, suggesting their potential as antitumor agents.

6-Cl-AA demonstrated a stronger inhibitory effect on certain chemotherapy-resistant cancer cells, such as HeLa cells resistant to cisplatin and SK-BR-3 cells resistant to doxorubicin, indicating its potential for treating resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid and 6-deoxy-6-chloro-ascorbic acid: potential anticancer drugs. Osmak, M., Kovacek, I., Ljubenkov, I., et al.[2013]

A 56-year-old lung cancer patient who received high-dose intravenous Vitamin C (up to 75 grams) three times a week for over a year showed stable CEA levels, suggesting potential benefits in managing cancer progression.

The case supports the idea that high-dose Vitamin C infusions can be safe and possibly effective in cancer treatment, as they may achieve plasma levels that are toxic to tumor cells without causing significant side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose intravenous vitamin c treatment in a patient with lung cancer: A case report. González, MJ., Berdiel, MJ., Miranda-Massari, JR., et al.[2022]

In a study involving 14 patients with stage IV pancreatic cancer, intravenous ascorbic acid was administered alongside standard chemotherapy (gemcitabine and erlotinib) for eight weeks, with nine patients completing the treatment.

The addition of ascorbic acid did not increase toxicity compared to standard treatment alone, and seven out of nine patients showed stable disease, indicating potential benefits that warrant further investigation in a phase II study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. Monti, DA., Mitchell, E., Bazzan, AJ., et al.[2022]

High-dose vitamin C therapy is gaining renewed interest in cancer treatment due to emerging evidence suggesting it may be effective when administered under the right protocols.

Research on the pharmacokinetics and mechanisms of action of ascorbate against tumor cells indicates that vitamin C deserves further investigation in the context of cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. Ohno, S., Ohno, Y., Suzuki, N., et al.[2022]

Ascorbic acid (AA) shows strong anticancer effects against non-small cell lung cancer (NSCLC) cells at pharmacologic doses, causing complete cell death at concentrations of 0.5 to 5 mM, while having minimal impact on normal lung epithelial cells.

Combining AA with the glycolysis inhibitor 3-PO enhances cell death in NSCLC cells through a synergistic effect that activates apoptosis via a reactive oxygen species (ROS)-dependent mechanism, suggesting that this combination could be a promising adjuvant therapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. Vuyyuri, SB., Rinkinen, J., Worden, E., et al.[2021]

In a study of 136 patients with advanced non-small-cell lung cancer, combining high-dose antioxidants (vitamins C, E, and beta-carotene) with chemotherapy (paclitaxel and carboplatin) resulted in a slightly higher overall response rate (37%) compared to chemotherapy alone (33%), but the difference was not statistically significant.

The median survival time was 11 months for the combination group versus 9 months for the chemotherapy-only group, indicating that while antioxidants did not harm the effectiveness of chemotherapy, larger studies are needed to confirm any potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. Pathak, AK., Bhutani, M., Guleria, R., et al.[2019]

In a study of 158 samples from 139 lung cancer patients, 64% had low plasma vitamin C levels, indicating a significant deficiency that could be linked to the disease and its treatment, particularly in the first 6 months post-surgery.

Lung tumors contained higher levels of vitamin C compared to normal lung tissue, suggesting that vitamin C may play a role in immune responses against tumors, and the authors recommend testing vitamin C supplementation in clinical trials to assess its impact on survival in lung cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hypovitaminosis C in lung-cancer patients: the utilization of vitamin C in surgical repair and lymphocyte-related host resistance. Anthony, HM., Schorah, CJ.[2019]

The combination of vitamin C with cisplatin significantly enhances the cytotoxic effects against gastric cancer cells, allowing for effective treatment with lower doses of cisplatin.

Co-treatment with vitamin C not only increases the number of cancer cells undergoing apoptosis (cell death) but also alters the cell cycle, promoting more effective cancer cell elimination compared to cisplatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic Effect of Vitamin C with Cisplatin for Inhibiting Proliferation of Gastric Cancer Cells Ghavami, G., Sardari, S.[2020]

In a phase I clinical trial involving 9 patients with stage IV pancreatic adenocarcinoma, pharmacological ascorbate (vitamin C) combined with gemcitabine was found to be well tolerated, with few adverse effects reported.

The treatment resulted in significantly higher plasma ascorbate levels and a mean survival of 13 months for patients who completed at least two cycles, suggesting potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Welsh, JL., Wagner, BA., van't Erve, TJ., et al.[2022]

Ascorbic acid (vitamin C) plays a crucial role in enhancing the body's resistance to cancer by stabilizing tissue and supporting immune functions, which may help protect against cancer progression.

Recent clinical trials suggest that supplemental ascorbate could have therapeutic value in cancer treatment, potentially leading to its inclusion in standard cancer care protocols in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C and cancer: an overview. Cameron, E.[2013]

Vitamin C intake from natural sources may help prevent certain types of cancer, such as pulmonary and breast cancer, and shows potential to enhance the effectiveness of cancer treatments like gemcitabine and erlotinib in pancreatic cancer.

Despite some promising results, the overall role of vitamin C in cancer prevention remains unclear, as it was not linked to cancer prevention in a Mendelian randomized study, highlighting the need for further clinical trials to establish its therapeutic benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review. Villagran, M., Ferreira, J., Martorell, M., et al.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8557029/

High-dose intravenous vitamin C, a promising multi-targeting ...

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC).

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352304225002314

High-dose vitamin C: A promising anti-tumor agent, insight ...

High-dose vitamin C exhibits selective anti-tumor effects, including pro-oxidative cytotoxicity, anti-cancer epigenetic regulation, and immune modulation.

3.

imrpress.com

imrpress.com/journal/IJVNR/95/3/10.31083/IJVNR37372/pdf

A Systematic Review a

Their results showed that intravenous vitamin C (IVC) combined with chemotherapy had no significant impact on progression- free survival (PFS) ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7190757/

A randomized phase II trial of best supportive care with or ...

High-dose vitamin C is also applied for lung cancer. It decreases cell proliferation in lung cancer cell lines [11], including mechanisms of cell cycle arrest [ ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03146962

High Dose Vitamin C Intravenous Infusion in Patients With ...

This is a multicenter, single arm, 3-cohort, open-label trial of high dose Vitamin C intravenous infusion in subjects with solid tumor malignancies who are ...

6.

cancer.gov

cancer.gov/about-cancer/treatment/cam/hp/vitamin-c-pdq

Intravenous Vitamin C (PDQ®)–Health Professional Version

Intravenous vitamin C, with and without conventional cancer therapies, appeared promising in early studies and was well tolerated.

7.

cdn.clinicaltrials.gov

cdn.clinicaltrials.gov/large-docs/94/NCT03799094/Prot_SAP_000.pdf

Clinical outcomes of intravenous vitamin C synergy with ...

Intravenous VitC in combination with TKI can significantly prolong the time of drug resistance, improve the quality of life, and have a positive ...