Uveal melanoma (UM) is the most common type of cancer inside the eyes of adults. Almost half of all patients diagnosed with UM will eventually develop metastases. Once metastases occur, the median patient survival is short.
In this trial, we will test if treatment with Melatonin after primary tumor diagnosis can prevent or delay the development of metastases. 100 patients diagnosed with primary UM will be randomized to either treatment with Melatonin tablets (20 mg at night), or to a control group. Both groups will be followed for 5 years. At 5 years, the number of patients that have developed metastases in the Melatonin and control groups will be compared (primary outcome measure).
The patient is ≥18 years
The patient has given his/her written informed consent to participate in the trial.
The patient has a melanoma originating in the choroid or in the ciliary body, as diagnosed by clinical methods and/or histological examination.
The patient's tumor is of size category T3d or higher, or stage IIIB or IIIC according to the American Joint Committee on Cancer (AJCC, version 8) criteria.
Oversensitivity or allergy to Melatonin or any of the excipients in the tablet.
The patient has metastatic disease, detectable with radiological examinations or any other method (development of metastases after recruitment to the trial does not disqualify the patient from participation).
The patient is unable to provide informed consent.
The patient has decreased liver function (e.g., liver cirrhosis or hepatitis)
Parallel
Melatonin
DrugWhite round tablets, each with a dose of 5 mg Melatonin. 4 tablets taken simultaneously at night. Tablets can be crushed and/or taken with a glass of water if the patient wish.
Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as relative risk (RR).
Measured as relative risk (i.e., the incidence rate of metastasis in the Melatonin arm divided by the incidence rate in the control group), with 95 % confidence interval.
Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as Cox regression hazard ratio (HR).
Measured as hazard ratio (i.e., the hazard for metastasis in the Melatonin arm divided by the hazard in the control group) with relevant covariates (e.g., tumor size, patient age, BAP-1 expression), with 95 % confidence interval.
Overall survival (OS) time from randomization in Melatonin vs. Control arm, evaluated with the Log-rank test.
Overall survival (the length of time from randomization that patients are still alive) in the Melatonin vs. Control arm. A Kaplan-Meier-curve will be drawn and the Log-rank test will be applied.
Overall survival (OS) time from the detection of metastasis in Melatonin vs. Control arm, evaluated with the Log-rank test.
Overall survival (the length of time from radiological detection of metastases that patients are still alive) in the Melatonin vs. Control arm. A Kaplan-Meier-curve will be drawn and the Log-rank test will be applied.
Number of patients that develop other cancers (i.e., cancer diagnoses other than uveal melanoma) in Melatonin vs. Control arm, evaluated as relative risk (RR).
Measured as relative risk (i.e., the incidence rate of other cancers in the Melatonin arm divided by the incidence rate in the control group), with a 95 % confidence interval.
Interim analysis: Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as relative risk (RR).
Measured as relative risk (i.e., the incidence rate of metastasis in the Melatonin arm divided by the incidence rate in the control group), with 95 % confidence interval.
Interim analysis: Overall survival (OS) in Melatonin vs. Control arm, evaluated with the Log-rank test.
Overall survival in the Melatonin vs. Control arm
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Gustav Stalhammar
Lead sponsor
St. Erik Eye Hospital
Sponsor institution
Karolinska Trial Alliance
Collaborator
The Swedish Eye Foundation (Ögonfonden)
Collaborator
The Swedish Society of Medicine
Collaborator
Swedish Cancer Foundation
Collaborator
