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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a Vitamin B5 supplement, taken with immunotherapy, can enhance treatment for melanoma, a type of skin cancer. It specifically targets patients whose melanoma cannot be surgically removed or has spread to other parts of the body. Participants should be newly diagnosed with advanced melanoma and have not started any previous systemic treatments. The goal is to determine if this combination can boost Vitamin B5 levels in the blood and affect the immune system. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Vitamin B5, or pantothenic acid, is generally safe for people. While few studies have explored its interaction with immunotherapy, Vitamin B5 plays a crucial role in many body functions and is present in foods like meat and vegetables. Previous research has not identified any major safety concerns regarding Vitamin B5.

For the immunotherapy drugs used in this trial, nivolumab and ipilimumab, existing evidence indicates they are generally safe but can cause side effects. Common side effects include tiredness and skin reactions, though serious side effects occur less frequently.

As this trial is in its early stages, the primary goal is to assess safety. Researchers will closely monitor participants for any side effects or adverse reactions to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for skin cancer, which typically involve surgery, radiation, or chemotherapy, C-PAN is a unique combination of Vitamin B5 and immunotherapy. Researchers are excited about C-PAN because it is taken orally, which can be more convenient and less invasive than traditional methods. Additionally, C-PAN works alongside immunotherapy drugs like Nivolumab and Ipilimumab, potentially boosting the body’s own immune response to target cancer cells more effectively. This novel approach could offer a new pathway for enhancing the effectiveness of existing immunotherapy treatments.

What evidence suggests that this treatment might be an effective treatment for melanoma?

Research has shown that Vitamin B5, also known as calcium pantothenate, might help the body fight cancer. Studies have found that this vitamin can enhance cancer treatments in mice by aiding the immune system in identifying and attacking cancer cells. This trial will evaluate the effectiveness of Vitamin B5, referred to as C-PAN, in combination with standard-of-care immunotherapy treatments Nivolumab and Ipilimumab for skin cancer. The idea is that Vitamin B5 helps the immune system's "watchdogs" spot and fight cancer more effectively. Although more research is needed, early results are promising for its use alongside regular cancer treatments. ^{1 3 6 7 8}

Who Is on the Research Team?

Samuel Saibil, MD

Principal Investigator

The Princess Margaret Cancer Foundation

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

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 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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06377111

NCT06377111 | A Study to Test the Benefit of Vitamin B5 in ... This single-center, single-cohort study aims to investigate the effectiveness of oral calcium pantothenate (C-PAN) in raising plasma pantothenic acid levels in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8794238/

Immunostimulatory effects of vitamin B5 improve anticancer ... These finding suggest that vitamin B5 is yet another B vitamin that stimulates anti-cancer immunosurveillance.

3. ctv.veeva.com ctv.veeva.com/study/a-study-to-test-the-benefit-of-vitamin-b5-in-patients-with-melanoma

A Study to Test the Benefit of Vitamin B5 in Patients With ... This single-center, single-cohort study aims to investigate the effectiveness of oral calcium pantothenate (C-PAN) in raising plasma pantothenic ...

4. researchgate.net researchgate.net/publication/358105672_Immunostimulatory_effects_of_vitamin_B5_improve_anticancer_immunotherapy

(PDF) Immunostimulatory effects of vitamin B5 improve ... Supplementation with vitamin B5 increases the efficacy of PD-L1-targeted cancer immunotherapy in mice, and the culture of T cells with CoA in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12133511/

Vitamin B5 and vitamin U review: justification of combined use ... This review delves into the current understanding of the impact of these vitamins on the gastrointestinal system, analyzing their mechanisms of action.

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/478677

A Study to Test the Benefit of Vitamin B5 in Patients With ... 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 ...

7. nature.com nature.com/articles/s42255-023-00915-7

Vitamin B5 supports MYC oncogenic metabolism and ... We show that pantothenic acid (vitamin B 5 ) associates with MYC-high areas within both human and murine mammary tumors, where its conversion to coenzyme A ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12067739/

Micronutrients and skin cancer risk - PubMed Central - NIH This study highlights that Selenium and Potassium may protect against MM, while Calcium increases NMSC risk, with Vitamin B6 providing protection against NMSC.