Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06377111
Other study ID # PANTHEON-IO
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date May 2024
Est. completion date May 2026

Study information

Verified date April 2024
Source University Health Network, Toronto
Contact Minge Xu
Phone 416-946-4501
Email minge.xu@uhn.ca
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 12
Est. completion date May 2026
Est. primary completion date May 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Dietary Supplement:
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.
Biological:
Nivolumab
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
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.

Locations

Country Name City State
Canada University Health Network- Princess Margaret Cancer Centre Toronto Ontario

Sponsors (1)

Lead Sponsor Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type Measure Description Time frame Safety issue
Other Correlation between change in pantothenic acid plasmatic level in mcMol/L between baseline and first day of ICI, 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 peripheral blood mononuclear cells examined using flow cytometry, CyTOF and other in vitro immunological assays at first day of ICI. 2 weeks
Other Correlation between change in plasmatic pantothenic acid level between baseline and week 9 assessment, and immune profiling. 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. 9 weeks
Primary To determine if the dose of 2000 mg daily of pantothenic acid achieves an increase in plasmatic concentration of pantothenic acid by at least a 50% between baseline and week 9, in 9 or more of the patients treated with combined ICI. Blood samples will be collected at baseline, and at week 9 to evaluate level in plasmatic pantothenic acid level, measured in mcMol/L. 9 weeks
Secondary Evaluate the overall response rate (ORR) of the enrolled cohort. ORR by RECIST V1.1 and iRECIST. 1 year
Secondary Evaluate the progression free survival (PFS) of the enrolled cohort. Measured by RECIST v1.1 and iRECIST. 1 year
Secondary Incidence of immune-related colitis. Immune-related colitis will be assessed by CTCAE version 5. 1 year
Secondary Correlation between baseline intestinal microbiome composition to the development of immune-related colitis. Correlation between bacteria taxa composition obtained through 16S rRNA sequencing and immune-related colitis. 1 year
Secondary Correlation between the early changes in composition of intestinal microbiome and the development of 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.. 1 year
Secondary The incidence of treatment-related adverse events. 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. 1 year
Secondary The incidence of treatment-related adverse events Correlation between baseline pantothenic acid plasmatic level in mcMol/L and ORR by RECIST and iRECIST. 1 year
Secondary Correlation between change in plasmatic pantothenic acid level between baseline and at first day of ICI, and ORR. Correlation between change in pantothenic acid plasmatic level in mcMol/L between baseline and first day of ICI, and ORR by RECIST and iRECIST. 1 year
See also
  Status Clinical Trial Phase
Completed NCT04062032 - Metabolomic and Inflammatory Effects of Oral Aspirin (ASA) in Subjects at Risk for Melanoma Phase 2
Completed NCT03620019 - Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma Phase 2
Active, not recruiting NCT03291002 - Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC Phase 1
Completed NCT04534309 - Behavioral Weight Loss Program for Cancer Survivors in Maryland N/A
Completed NCT00962845 - Hydroxychloroquine in Patients With Stage III or Stage IV Melanoma That Can Be Removed by Surgery Early Phase 1
Completed NCT00324623 - Cyclophosphamide and Fludarabine Followed by Cellular Adoptive Immunotherapy and Vaccine Therapy in Patients With Metastatic Melanoma Phase 1
Completed NCT00096382 - Cyclophosphamide, Fludarabine, and Total-Body Irradiation Followed By Cellular Adoptive Immunotherapy, Autologous Stem Cell Transplantation, and Interleukin-2 in Treating Patients With Metastatic Melanoma Phase 2
Completed NCT00104845 - Vaccine Therapy in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Melanoma Phase 1
Completed NCT00072124 - Dacarbazine and/or Cisplatin Compared With Complete Metastasectomy in Treating Patients With Stage IV Melanoma Phase 3
Completed NCT00089193 - Vaccine Therapy With or Without Sargramostim in Treating Patients With Stage IIB, Stage IIC, Stage III, or Stage IV Melanoma Phase 2
Completed NCT00072085 - Immunization With gp100 Protein Vaccine in Treating Patients With Metastatic Melanoma Phase 2
Active, not recruiting NCT00039234 - Interleukin-2 With or Without Histamine Dihydrochloride in Treating Patients With Stage IV Melanoma Metastatic to the Liver Phase 3
Completed NCT00049010 - Diagnostic Study to Predict the Risk of Developing Metastatic Cancer in Patients With Stage I or Stage II Melanoma N/A
Completed NCT00042783 - Vaccine Therapy in Treating Patients With Stage IV Melanoma Phase 2
Completed NCT00020358 - Vaccine Therapy in Treating Patients With Melanoma Phase 2
Completed NCT00005610 - Study of Aerosolized Sargramostim in Treating Patients With Melanoma Metastatic to the Lung Phase 2
Completed NCT00006385 - Vaccine Therapy With or Without Biological Therapy in Treating Patients With Metastatic Melanoma Phase 2
Completed NCT00006022 - Interleukin-2 Plus Bryostatin 1 in Treating Patients With Melanoma or Kidney Cancer Phase 1
Recruiting NCT03767348 - Study of RP1 Monotherapy and RP1 in Combination With Nivolumab Phase 2
Withdrawn NCT00006126 - Peripheral Stem Cell Transplantation in Treating Patients With Melanoma or Small Cell Lung, Breast, Testicular, or Kidney Cancer That is Metastatic or That Cannot Be Treated With Surgery Phase 1