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

Trial Summary

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.

What data supports the effectiveness of the treatment Vitamin C for lung cancer?

Research suggests that Vitamin C may help the body's immune system fight cancer and could be beneficial in cancer treatment. It has shown potential in enhancing the effects of chemotherapy in other cancers, like pancreatic cancer, and may help stabilize tissues and support immune functions that resist cancer spread. ^{1 2 3 4 5}

Is high-dose Vitamin C safe for humans?

High-dose Vitamin C, given intravenously, has been used in cancer patients without causing harmful side effects, according to case reports. It is generally considered safe for humans at these doses, but more research is needed to confirm its safety when combined with other treatments. ^{6 7 8 9 10}

How does vitamin C treatment differ from other lung cancer treatments?

Vitamin C treatment for lung cancer is unique because it may enhance the body's immune response and help in surgical recovery by increasing vitamin C levels, which are often low in lung cancer patients. It also shows potential as an anticancer agent, especially when used in high doses or combined with other treatments, targeting cancer cell metabolism without harming normal cells. ^{2 5 6 7 11}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 (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]

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]

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]

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]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Vitamin C and cancer: an overview. [2013]

2. England 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. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

The Role of Vitamin C in Cancer Prevention and Therapy: A Literature Review. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy alone vs. chemotherapy plus high dose multiple antioxidants in patients with advanced non small cell lung cancer. [2019]

5. Germany 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Ascorbic acid and a cytostatic inhibitor of glycolysis synergistically induce apoptosis in non-small cell lung cancer cells. [2021]

7. Slovakia pubmed.ncbi.nlm.nih.gov

Ascorbic acid and 6-deoxy-6-chloro-ascorbic acid: potential anticancer drugs. [2013]

8. Greece pubmed.ncbi.nlm.nih.gov

High-dose vitamin C (ascorbic acid) therapy in the treatment of patients with advanced cancer. [2022]

9. England pubmed.ncbi.nlm.nih.gov

High dose intravenous vitamin c treatment in a patient with lung cancer: A case report. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. [2022]

11. Iran pubmed.ncbi.nlm.nih.gov

Synergistic Effect of Vitamin C with Cisplatin for Inhibiting Proliferation of Gastric Cancer Cells [2020]