Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Bone Density Conservation Agents

Hematinics

Vitamins

Nivolumab

Antibodies

Antibodies, Monoclonal

Immune Checkpoint Inhibitors

Immunomodulating Agents

Calcium

Ipilimumab

Immunoglobulins

Vitamin B Complex

Calcium, Dietary

Pantothenic Acid

Immunoglobulins, Intravenous

Trace Elements

Immunologic Factors

Antineoplastic Agents, Immunological

Folic Acid

Vitamin B5

Folate

Vitamin B9

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.

C-PAN is an essential nutrient as it is required for the synthesis of CoA, a key cofactor in the tricarboxylic acid cycle and fatty acid metabolism, as well as for the synthesis of acyl carrier protein. Pantothenate appears to be safe in humans with studies describing the administration of doses up to 10 grams per day over prolonged periods of time; hence, no upper limit for tolerability has been established. In this study, oral supplement consisting of 2000 mg daily of C-PAN will be administered to a single cohort of patients.

C-PAN

Nivolumab is an ICI, a type of immunotherapy. It is a monoclonal antibody that binds to the protein PD-1 on the surface of immune cells called T cells. Nivolumab 1 mg/kg every 3 weeks for up to 4 cycles (upon patient´s tolerability) followed by maintenance Nivolumab 3 mg/kg (or fixed dose 240 mg) every 2 weeks or Nivolumab 6 mg/kg (or fixed dose 480 mg) every 4 weeks.

Ipilimumab is an ICI, a type of immunotherapy. It is a monoclonal antibody that binds to the protein CTLA-4 on immune cells called T cells. Ipilimumab 3 mg/kg every 3 weeks for up to 4 cycles.

Minge Xu

Samuel Saibil

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.

This single-center, single-cohort study aims to investigate the effectiveness of oral calcium pantothenate (C-PAN) in raising plasma pantothenic acid levels in melanoma patients. Conducted at Princess Margaret Cancer Centre, the study will enroll 12 eligible subjects with locally unresectable or metastatic melanoma undergoing first-line standard of care (SOC) with combined immune checkpoint inhibitor (ICI) therapy, Nivolumab and Ipilimumab. Additionally, the study will explore changes in immune cell subsets, metabolomics, and gut microbiome to understand the impact of pantothenate/CoA pathway manipulation on ICI efficacy and immune-mediated colitis prevention.

Patients will initially receive a run-in period of C-PAN at a dose of 2000 mg daily for 3 to 7 days, alongside approved SOC drugs. Subsequently, patients will continue with the maintenance dose of 2000 mg daily, starting on the same day as the first cycle of combined ICI. This maintenance dose will be continued until the occurrence of unacceptable toxicity, disease progression by iRECIST criteria, or for a maximum duration of 1 year, whichever comes first, unless there are specific criteria indicating the discontinuation of C-PAN.

For all subjects, radiologic imaging to assess response to treatment will be performed as per standard practice (ideally every 8 to 12 weeks, with first assessment at week 9). Fecal samples will be collected from all subjects at baseline (1st sample), at week 9 following the start of ICI, and at study completion or discontinuation. An additional fecal sample will be collected in case of development of immune-related colitis or immune-related diarrhea.

Standard laboratory investigations for immunotherapy will be collected as per institutional practice. Blood samples for biomarkers will be collected at various time points.

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

Phase 1 Trial of PANtoTHEnic Acid in Patient With Metastatic or Unresectable Melanoma ON ImmunOtherapy (PANTHEON-IO)

Correlation between change in pantothenic acid plasmatic level in mcMol/L between baseline and first day of ICI, and peripheral blood mononuclear cells examined using flow cytometry, CyTOF and other in vitro immunological assays at first day of ICI.

Correlation between change in pantothenic acid plasmatic level in mcMol/L between baseline and week 9 assessment, and peripheral blood mononuclear cells examined using flow cytometry, CyTOF and other in vitro immunological assays.

Blood samples will be collected at baseline, and at week 9 to evaluate level in plasmatic pantothenic acid level, measured in mcMol/L.

Immune-related colitis will be assessed by CTCAE version 5.

Correlation between bacteria taxa composition obtained through 16S rRNA sequencing and immune-related colitis.

Correlate changes in bacteria taxa composition obtained through 16S rRNA sequencing from baseline samples to early time-point (week 9), with the development of immune-related colitis..

All adverse events that are related to C-PAN and/or in the investigator's opinion is related to immunotherapy will be recorded, and graded as per CTCAE version 5.

Correlation between baseline pantothenic acid plasmatic level in mcMol/L and ORR by RECIST and iRECIST.

Correlation between change in pantothenic acid plasmatic level in mcMol/L between baseline and first day of ICI, and ORR by RECIST and iRECIST.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Test the Benefit of Vitamin B5 in Patients With Melanoma	NCT06377111	Melanoma (Skin)	C-PAN Nivolumab Ipilimumab	18 Years -	University Health Network, Toronto
A Study to Test the Benefit of Vitamin B5 in Patients With Melanoma	NCT06377111	Melanoma (Skin)	C-PAN Nivolumab Ipilimumab	18 Years -	University Health Network, Toronto

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