Vitamin B5 + Immunotherapy for Skin Cancer

Overseen By Minge Xu

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University Health Network, Toronto

Must be taking: Immunotherapy

Disqualifiers: Gastrointestinal disorders, Inflammatory bowel disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

Duration: Up to 1 year

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinator or your doctor.

What data supports the effectiveness of the treatment C-PAN, Calcium Pantothenate, Vitamin B5, Pantothenic acid for skin cancer?

Research suggests that Vitamin B5 (pantothenic acid) can enhance the effectiveness of cancer immunotherapy by boosting the activity of certain immune cells. In a small group of melanoma patients, higher levels of Vitamin B5 were linked to better responses to immunotherapy, and in mice, Vitamin B5 improved the success of cancer treatments targeting specific immune checkpoints. ^{1 2 3 4 5}

Is Vitamin B5 safe for use in humans?

Vitamin B5, also known as calcium pantothenate, is generally safe for humans, but there have been rare cases of allergic reactions, such as skin rashes, in some individuals. In animal studies, it has shown protective effects on the skin and liver without causing harmful changes. ^{4 5 6 7 8}

How does the Vitamin B5 + Immunotherapy treatment for skin cancer differ from other treatments?

This treatment is unique because it combines Vitamin B5, which enhances the body's immune response by promoting the development of specific immune cells, with immunotherapy, potentially increasing its effectiveness against skin cancer. This approach leverages the immunostimulatory effects of Vitamin B5 to improve the outcomes of existing immunotherapy treatments. ^{1 4 6 9 10}

What is the purpose of this trial?

This study is open to patients with a type of cancer called melanoma. Patients can join the study if their tumor cannot be removed by surgery or has spread to other organs, and are planned to receive immunotherapy as treatment for their cancer. This study is looking at whether taking calcium pantothenate supplement (a type of Vitamin B5) can increase its levels in the blood and have an effect in the immune system, when its used in combination with the immunotherapy.

Research Team

Samuel Saibil, MD

Principal Investigator

The Princess Margaret Cancer Foundation

Eligibility Criteria

This trial is for melanoma patients whose cancer can't be surgically removed or has spread. They should be scheduled to receive immunotherapy. The study aims to see if Vitamin B5 supplements can boost the immune system when combined with standard treatments.

Inclusion Criteria

Not pregnant for females of childbearing potential as indicated by negative serum or urine pregnancy test within 72 hours of study start

I haven't had treatments like chemotherapy for my advanced melanoma.

I can take care of myself and perform daily activities.

Exclusion Criteria

Pregnant or planning to get pregnant in the next 6 months

Any condition that, in the opinion of the Investigator, would interfere with subject safety, or evaluation of the collected specimen and interpretation of study result

I have inflammatory bowel disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in Period

Participants receive C-PAN at a dose of 2000 mg daily for 3 to 7 days alongside standard of care drugs

1 week

Treatment

Participants continue with a maintenance dose of C-PAN 2000 mg daily in combination with ICI therapy until unacceptable toxicity, disease progression, or for a maximum of 1 year

Up to 1 year

Radiologic imaging every 8 to 12 weeks, with first assessment at week 9

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• C-PAN

Trial Overview The trial is testing the addition of a Vitamin B5 supplement, calcium pantothenate, alongside two immunotherapies: Ipilimumab and Nivolumab. It's examining whether this vitamin can enhance blood levels and potentially improve immune response in melanoma treatment.

Participant Groups

Group I: C-PAN in combination with ICI Experimental Treatment 3 Interventions

C-PAN will be taken orally once daily in the morning prior to eating. The daily oral dose of C-PAN is 2000 mg (4 capsules of 500 mg each). Subjects will receive C-PAN exclusively for a run-in period of 3 to 7 days, and then a maintenance dose as long as the patient continues to receive SOC Nivolumab and Ipilimumab. Treatment will continue until unacceptable toxicity, progression of disease (PD), start of new anticancer therapy, or for a maximum of 1 year, whichever occurs earlier, and in the absence of criteria to discontinue C-PAN.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

In a study involving 58 patients with actinic keratoses (AKs), high-dose oral vitamin D3 (10,000 IU daily) significantly improved the clearance rates of AK lesions when combined with photodynamic therapy (PDT), achieving a clearance rate of 72.5% compared to 54.4% in the control group.

Patients with vitamin D3 deficiency had lower clearance rates (40.9%) compared to those with normal levels (62.6%), suggesting that vitamin D3 plays a crucial role in enhancing the effectiveness of PDT for treating AKs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. Bullock, TA., Negrey, J., Hu, B., et al.[2023]

In a preliminary study of 9 patients with high-risk uveal melanoma, the addition of oral biological dietary adjuvants after standard treatment resulted in a 100% local tumor control rate and no recurrence of disease over a mean follow-up of 80 months.

This approach showed significantly better outcomes compared to similar patients receiving standard care alone, suggesting that oral biological components may help address underlying deficiencies associated with melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of the recurrence-free interval using biological adjuvant therapy in uveal melanoma. Tallberg, T., Uusitalo, R., Sarna, S., et al.[2006]

In a study of 501 patients with advanced cancer, elevated serum vitamin B12 levels were found to negatively impact overall survival and progression-free survival in patients treated with immune checkpoint inhibitors, suggesting that high VitB12 may hinder the effectiveness of this immunotherapy.

The analysis indicated that while elevated VitB12 was a negative predictor for outcomes specifically in the immune checkpoint inhibitor group, further research is necessary to understand the underlying mechanisms and potential strategies to improve immunotherapy responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Too Much of a Good Thing: The Association of Elevated Vitamin B12 Levels and Outcomes in Patients With Cancer Treated With Immunotherapy. Turgeman, I., Benaim, AR., Regev-Tsur, S., et al.[2023]

Vitamin B5 (pantothenic acid) enhances the differentiation of CD8+ T cells into IL-22-producing Tc22 cells, which may improve their ability to fight cancer by boosting mitochondrial metabolism.

In melanoma patients, higher plasma levels of vitamin B5 are associated with better responses to PD-1-targeted immunotherapy, and in mice, vitamin B5 supplementation improves the effectiveness of PD-L1-targeted cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunostimulatory effects of vitamin B5 improve anticancer immunotherapy. Bourgin, M., Kepp, O., Kroemer, G.[2022]

In a study of 203 adults with a history of multiple non-melanoma skin cancers, patients were willing to accept a 23% reduction in skin cancer risk with a modest increase in cost, but they were not willing to accept a significant increase in severe infection risk associated with nicotinamide supplementation.

The findings suggest that while nicotinamide can reduce skin cancer risk, the potential for increased severe infections may deter patients from choosing this treatment, indicating a need for careful consideration of patient preferences in treatment recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. Boeri, M., Skelsey, MK., Schiro, JA., et al.[2023]

A 53-year-old female nurse's aide developed intermittent facial eruptions due to sensitization from calcium pantothenate, which is commonly used in cosmetics for its anti-static and hair conditioning properties.

This case is notable as it is one of the few documented instances of sensitization to calcium pantothenate, highlighting the potential for allergic reactions to this ingredient in cosmetic products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Calcium pantothenate is present in cosmetics and may cause allergic contact dermatitis. Pastor-Nieto, MA., Gatica-Ortega, ME., Sánchez-Herreros, C., et al.[2021]

The oral formulation Panto[vi]gar®, containing l-cystine and thiamin, significantly enhances the proliferation and metabolic activity of normal human epidermal keratinocytes (NHEKs), suggesting its potential effectiveness in treating conditions like diffuse hair loss.

Panto[vi]gar® also demonstrates a protective effect against UV radiation, as cells treated with the formulation showed only a 12-18% reduction in metabolic activity after UV exposure, compared to a 72% reduction in untreated cells, indicating its role in cellular protection against UV damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cystine-thiamin-containing hair-growth formulation modulates the response to UV radiation in an in vitro model for growth-limiting conditions of human keratinocytes. Hengl, T., Herfert, J., Soliman, A., et al.[2019]

In a study involving Wistar rats, calcium pantothenate was administered at a dose of 180 mg/day for 42 days, showing no ultrastructural changes in the epidermis, indicating its safety in this context.

Calcium pantothenate provided significant protection to both the liver and epidermis from the harmful effects of radiation, suggesting it may be an effective radioprotective agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electron-microscopic studies on the effect of calcium pantothenate upon rat liver and locally irradiated epidermis. Craciun, C., Ghircoiasiu, M., Craciun, V.[2013]

In a study involving DMBA-treated hairless mice exposed to UVB radiation over 18 weeks, a high dietary level of vitamin B6 (35 mg/kg) significantly increased the incidence and number of skin tumors compared to a lower level (1 mg/kg).

Despite the increase in tumorigenesis, the higher vitamin B6 diets did not affect oxidative stress markers in the skin, indicating that the mechanism by which vitamin B6 exacerbates tumor formation may not be related to oxidative stress.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementing vitamin B6 to a low vitamin B6 diet exaggerates UVB-induced skin tumorigenesis in DMBA-treated hairless mice. Lu, T., Xu, Y., Monttinen, ES., et al.[2019]

Certain B vitamin supplements, like cyanocobalamin, pyridoxine, and riboflavin, may worsen acne and cause allergic reactions, indicating that vitamin supplementation should be approached with caution in skin conditions.

Niacinamide shows promise as a treatment for acne and hyperpigmentation, and vitamin B3 may also help in preventing nonmelanoma skin cancer, highlighting the potential benefits of specific vitamins in dermatological therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin B group levels and supplementations in dermatology. Elgharably, N., Al Abadie, M., Al Abadie, M., et al.[2023]

References

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

Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. [2023]

2. Greece pubmed.ncbi.nlm.nih.gov

Improvement of the recurrence-free interval using biological adjuvant therapy in uveal melanoma. [2006]

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

Too Much of a Good Thing: The Association of Elevated Vitamin B12 Levels and Outcomes in Patients With Cancer Treated With Immunotherapy. [2023]

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

Immunostimulatory effects of vitamin B5 improve anticancer immunotherapy. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Patients' willingness to accept adverse event and cost tradeoffs from oral nicotinamide for reduced risk of non-melanoma skin cancer. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Calcium pantothenate is present in cosmetics and may cause allergic contact dermatitis. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cystine-thiamin-containing hair-growth formulation modulates the response to UV radiation in an in vitro model for growth-limiting conditions of human keratinocytes. [2019]

8. Hungary pubmed.ncbi.nlm.nih.gov

Electron-microscopic studies on the effect of calcium pantothenate upon rat liver and locally irradiated epidermis. [2013]

9. Japan pubmed.ncbi.nlm.nih.gov

Supplementing vitamin B6 to a low vitamin B6 diet exaggerates UVB-induced skin tumorigenesis in DMBA-treated hairless mice. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

Vitamin B group levels and supplementations in dermatology. [2023]