Adjuvant Melatonin for Uveal Melanoma

• Status: Not yet recruiting
• Trial end date: 2031-01-01
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gustav Stalhammar
• Collaborators: Karolinska Trial Alliance; Swedish Cancer Society; The Swedish Eye Foundation (Ögonfonden); The Swedish Society of Medicine
• Treatments: Melatonin

Criteria

Inclusion Criteria:

1. The patient is ≥18 years

2. The patient has given his/her written informed consent to participate in the trial.

3. The patient has a melanoma originating in the choroid or in the ciliary body, as diagnosed by clinical methods and/or histological examination.

AND at least one of the following 7 items:

4. 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.

5. The patient's tumor is large according to modified criteria from the Collaborative Ocular Melanoma Study (COMS), i.e. largest basal diameter >16 mm or apical thickness >8 mm.

6. The patient's tumor was of size category T2a before plaque brachytherapy and has then recurred.

7. The patient's tumor has an epithelioid cell type (>5 epithelioid cells per high power field and >90 % of tumor cells epithelioid).

8. The patient's tumor has a low immunohistochemical expression of BAP1.

9. The patient's tumor has more than 9 mitoses per high power field.

10. The patient has >60 % risk of metastases within 5 years, as determined with another published and validated prognostic test (e.g. gene expression class 2).

11. If the patient is already being treated with Melatonin, a two-week wash out period will be applied before randomization.

Exclusion Criteria:

1. Oversensitivity or allergy to Melatonin or any of the excipients in the tablet.

2. 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).

3. The patient is unable to provide informed consent.

4. The patient has decreased liver function (e.g., liver cirrhosis or hepatitis)

5. The patient is pregnant or a fertile woman (Women of child-bearing potential, WOCBP). Fertility is defined as the time between menarche and menopause for women that are not permanently sterile by hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. Menopause is defined as absence of menstruation for 12 months or longer without other cause.

6. The patient is breast feeding or is planning to breastfeed before the end of the trial. Women that are included in the trial and begin to breastfeed before the end of the trial must resign from the trial.

7. The patient has epilepsy.

8. The patient is being treated (for more than 4 weeks) with CYP1A2 inhibitors Fluvoxamine, Ciprofloxacin, Norfloxacin, or Verapamil, with combined hormonal contraception (containing etinylestradiole and progestin), with hormonal substitution therapy, with 5- or 8-metoxypsoralene or cimetidine. If a patient starts using any of these substances for more than 4 weeks after recruitment to the trial, he or she does not need to resign from the trial but may pause the use of Melatonin, and then restart after the use of the other substance has ceased. Concurrent treatment with CYP1A2 inducers including carbamazepine, fenytoine, rifampicin, omeprazole, calcium antagonists, benzodiazepine-related hypnotics, non-steroid anti-inflammatory drugs (NSAIDs) and beta blockers is not an exclusion criterium. Concurrent treatment with warfarin or other vitamin K antagonists is not an exclusion criterium, but requires information to the patient and discussion about dose adjustments with the prescribing physician.

9. The primary UM was diagnosed more than 12 months ago.