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

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

NCT ID: NCT06377111

Condition: Melanoma (Skin)

Conditions: Official terms:
Melanoma
Pantothenic Acid
Nivolumab
Ipilimumab
Antibodies
Immunoglobulins

Conditions: Keywords:
Vitamin B5
Unresectable melanoma
Metastatic melanoma
Pantothenic acid
Combined immune checkpoint inhibitors
ICI
Nivolumab
Ipilimumab
Anti-PD-1 antibody
Anti-CLTA-4 antibody
Skin cancer
Melanoma
Calcium pantothenate

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Dietary Supplement
Intervention name: C-PAN
Description: 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.
Arm group label: C-PAN in combination with ICI

Other name: Calcium Pantothenate

Other name: Vitamin B5

Intervention type: Biological
Intervention name: Nivolumab
Description: 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.
Arm group label: C-PAN in combination with ICI

Other name: anti-PD-1 antibody

Intervention type: Biological
Intervention name: Ipilimumab
Description: 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.
Arm group label: C-PAN in combination with ICI

Other name: anti-CLTA-4 antibody

Summary: 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.

Detailed description: 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.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - 1. Signed written and voluntary informed consent. - 2. Age ≥18 years, male or female. - 3. Have histologically or cytological documented unresectable stage III or stage IV metastatic melanoma (AJCC 8th edition). - 4. Have not received any previous systemic treatment for advanced melanoma, including chemotherapy, immunotherapy or targeted therapy. - 5. Be willing and able to provide stool and blood specimen for analyses at protocol specified time points. - 6. Performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale. - 7. Not pregnant for females of child bearing potential as indicated by negative serum or urine pregnancy test within 72 hours of study start Exclusion Criteria: - 1. Subjects unable to swallow orally administered medications or any subjects with gastrointestinal disorders likely to interfere with absorption (e.g. bowel obstruction, short gut syndrome, blind loop syndrome, ileostomy, etc.). Subjects with colostomies may be enrolled. - 2. Subjects with inflammatory bowel disease. - 3. 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. - 4. Pregnant or planning to get pregnant in the next 6 months. - 5. Female patient breastfeeding. - 6. Allergy to the investigational product (or its non-medicinal ingredients)- Calcium Pantothenate (stearic acid, Hydroxypropyl methylcellulose) or Immune checkpoint inhibitors (or its non-medicinal ingredients)- Nivolumab (Hydrochloric acid, mannitol (E421), pentetic acid, polysorbate 80, sodium chloride, sodium citrate, sodium hydroxide) and Ipilimumab (diethylene triamine pentaacetic acid (DTPA), mannitol, polysorbate 80, sodium chloride, Tris-hydrochloride, sodium hydroxide, hydrochloric acid

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: University Health Network- Princess Margaret Cancer Centre

Address:
City: Toronto
Zip: M5G 2M9
Country: Canada

Status: Recruiting

Contact:
Last name: Minge Xu

Phone: 416-946-4501

Phone ext: 7754
Email: minge.xu@uhn.ca

Investigator:
Last name: Samuel Saibil
Email: Principal Investigator

Start date: August 2024

Completion date: August 2026

Lead sponsor:
Agency: University Health Network, Toronto
Agency class: Other

Source: University Health Network, Toronto

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06377111