Using Melatonin to Prevent Metastases in Uveal Melanoma

Adjuvant Melatonin for Uveal Melanoma: A Randomized Open Phase III Study

This study is testing whether taking Melatonin at night can help people with uveal melanoma avoid or delay the spread of their cancer.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: St. Erik Eye Hospital (Academic / other)
• Locations: 1 site (Stockholm, Stockholm County)
• Trial ID: NCT05502900 on ClinicalTrials.gov

What this trial studies

This trial investigates the effectiveness of Melatonin as an adjuvant treatment for patients diagnosed with primary uveal melanoma (UM) to prevent or delay the onset of metastases. A total of 100 patients will be randomized to receive either Melatonin tablets at night or a control treatment, with follow-up conducted over five years. The primary outcome measure will be the comparison of metastasis development between the two groups at the end of the study period. The trial is conducted at St. Erik Eye Hospital in Stockholm, Sweden, which specializes in uveal melanoma treatment.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of primary uveal melanoma that is classified as high risk for metastasis.

Not a fit: Patients with low-risk uveal melanoma or those who have already developed metastases may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates for patients with uveal melanoma by delaying or preventing the development of metastases.

How similar studies have performed: While several trials have explored treatments for metastatic uveal melanoma, the use of Melatonin as an adjuvant therapy is a novel approach that has not been extensively tested.

Eligibility 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.

Where this trial is running

Stockholm, Stockholm County

• St. Erik Eye Hospital — Stockholm, Stockholm County, Sweden (Recruiting)

Study contacts

• Principal investigator: Gustav Stålhammar, MD PhD — St. Erik Eye Hospital and Karolinska Institutet
• Study coordinator: Gustav Stålhammar, MD PhD

Conditions Uveal Melanoma; Uveal Melanoma, Posterior, Medium/Large Size; Eye Cancer, Intraocular Melanoma; Melatonin; Adjuvant; Preventive; Uveal melanoma; Survival