Nicotinamide Chemoprevention for Keratinocyte Carcinoma in Solid Organ Transplant Recipients - Pivotal Trial

Improved survival after solid organ transplantation has created the need to better prevent the long-term adverse effects of immunosuppressant drugs in transplant survivors - particularly cancer development. Keratinocyte carcinoma (non-melanoma skin cancer) is by far the most common form of post-transplant malignancy and has a more aggressive clinical course than in the general population. Preventive measures are thus critical to reduce the burden of skin cancer in the high-risk transplant population.

Nicotinamide is a low-cost, commercially available, over-the-counter Vitamin B3 derivative that has been found to safely reduce the rate of keratinocyte carcinoma in immunocompetent patients with a history of skin cancer. It is unclear whether its efficacy and safety translate to the immunosuppressed transplant population.

Given this uncertainty, Investigators plan to build on our internal pilot study (N=120) to conduct the SPRINTR (Skin cancer PRevention with Nicotinamide in Transplant Recipients) pivotal trial to address these specific aims:

Primary question: Does oral nicotinamide (500 mg twice daily) reduce the rate of further keratinocyte carcinoma compared with placebo when used in addition to standard care for up to 208 weeks in high-risk solid organ transplant recipients?

Secondary questions:

1. What is the safety of nicotinamide when used in addition to standard care for up to 208 weeks in the transplant population? 2. What is the effect of nicotinamide on quality of life related to skin cancer?

Investigators will conduct a multicentre, pragmatic, parallel group, investigator- and patient-blinded, randomized trial with a superiority framework. This pivotal trial will evaluate the efficacy and safety of oral nicotinamide versus placebo to prevent further keratinocyte carcinoma in 396 high-risk solid organ transplant recipients. Data from our previous internal pilot study (N=120 participants) will be combined with data from the current pivotal trial (N=276 additional patients) in the final analysis.

• Time to first invasive squamous cell carcinoma during follow-up [Срок оценки: Up to 208 weeks]
• Time to first basal cell carcinoma during follow-up [Срок оценки: Up to 208 weeks]
• Time to multiple keratinocyte carcinomas over follow-up [Срок оценки: Up to 208 weeks]
• Occurrence of adverse events during follow-up [Срок оценки: 208 weeks]
• Acute graft rejection (biopsy-confirmed) [Срок оценки: 208 weeks]
• Graft loss or retransplantation [Срок оценки: 208 weeks]
• High/low cyclosporine or tacrolimus blood concentration requiring dose adjustment [Срок оценки: 208 weeks]
• Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [Срок оценки: 52 weeks]
• Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [Срок оценки: 104 weeks]
• Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [Срок оценки: 156 weeks]
• Change from baseline in annual Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) score [Срок оценки: 208 weeks]
• Neurocognitive substudy - Change from baseline in demographically-corrected T score for Montreal Cognitive Assessment (MoCA) [Срок оценки: 52 weeks]