AMUM trial -Adjuvant Melatonin for Uveal Melanoma: A randomized open Phase III Study

The primary objective of the AMUM trial is to evaluate whether **adjuvant treatment** with 20 mg of **melatonin** administered orally each evening for five years can reduce the incidence of metastases in patients with **uveal melanoma** over a five-year period. This is clinically relevant as metastasis significantly impacts prognosis and survival in uveal melanoma, a rare but aggressive form of eye cancer.

Secondary objectives include assessing whether the same melatonin regimen can:

• Improve overall survival at five years.
• Reduce the risk of developing other cancers within five years.
• Enhance overall survival following the detection of metastases.
• Determine if the incidence of adverse events (AEs) and serious adverse events (SAEs) differs between the melatonin and control groups.

The clinical trial involves participants diagnosed with **uveal melanoma**, a type of cancer that occurs in the eye. The study population includes both male and female subjects, aged 18 years and older. The trial does not focus on a vulnerable population. Participants were selected based on specific inclusion criteria, such as having a clinically or histopathologically diagnosed malignant melanoma originating from the choroid or ciliary body, and a high risk of developing metastases within five years. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits are not specified as part of the selection criteria. The trial aims to evaluate the effect of adjuvant treatment with melatonin on the incidence of metastases in this patient population over a five-year period.

The clinical trial is designed to evaluate the efficacy of **melatonin** as an adjuvant treatment for **uveal melanoma**. This is a randomized, open-label, Phase III study. The trial aims to determine whether a daily dose of 20 mg melatonin over a period of five years can reduce the incidence of metastases in patients with uveal melanoma. The study is expected to conclude by March 31, 2032, with recruitment having commenced on August 1, 2022.

Participants will be involved in the study for a maximum of five years, during which they will undergo a series of study visits. The initial visit will be a screening visit to confirm eligibility based on specific inclusion criteria, such as age and risk of metastasis. Following randomization, participants will be assigned to either the melatonin treatment arm or the control arm. Regular follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will occur at the conclusion of the five-year treatment period, or earlier if the participant withdraws or is withdrawn from the study.

Participants may be terminated early from the study if they experience significant adverse events, fail to adhere to the study protocol, or choose to withdraw their consent. The primary endpoint of the study is the proportion of participants free from metastases five years post-randomization. Secondary endpoints include overall survival, the risk of developing other cancers, and the incidence of adverse events. The study is conducted in accordance with regulatory guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the administration of **Melatonin AGB 5 mg tablets** as the experimental medication. The active substance in this formulation is **melatonin**, which is of chemical origin. The pharmaceutical form of the medication is a tablet, and it is intended for **oral** administration. Participants in the trial will receive a dosage of 20 mg of melatonin each evening. The maximum daily dose is set at 20 mg, with a total maximum dose of 36.5 grams over the course of the study. The treatment period is planned for a maximum of 60 months. The medication is manufactured by AGB-PHARMA AB and is not a pediatric formulation.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of the experimental medication, Melatonin AGB 5 mg tablets. Compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen. Participants' adherence to the medication schedule will be assessed regularly to maintain the integrity of the study data.

The efficacy of the clinical trial titled "AMUM trial - Adjuvant Melatonin for Uveal Melanoma: A randomized open Phase III Study" will be assessed using specific primary and secondary endpoints. The primary endpoint is the proportion of participants who remain free from **metastases** five years after randomization in both the melatonin and control arms, evaluated through relative risk. Secondary endpoints include overall survival five years post-randomization, analyzed using Kaplan-Meier curves and Log-rank tests; the risk of developing another cancer within five years post-randomization, assessed via Cox regression risk ratio; overall survival following the detection of metastases, also analyzed with Kaplan-Meier curves and Log-rank tests; and the proportion of participants experiencing adverse events (AE) and serious adverse events (SAE) in both the melatonin and control arms during the 0-5 year period post-randomization, evaluated through relative risk.