Adjuvant Melatonin for Uveal Melanoma

NCT05502900 | Recruiting Phase 3 DMC

• 2 other identifiers: AMUM v 2.02022-500307-49
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Uveal Melanoma; Uveal Melanoma, Posterior, Medium/Large Size; Eye Cancer, Intraocular Melanoma

Keywords

Melatonin; Adjuvant; Preventive; Uveal melanoma; Survival; Phase 3 trial

Outcome Measures

Primary Outcomes (1)

• 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.

  5 years

Secondary Outcomes (6)

• Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as Cox regression hazard ratio (HR).

  5 years

• Overall survival (OS) time from randomization in Melatonin vs. Control arm, evaluated with the Log-rank test.

  5 years

• Overall survival (OS) time from the detection of metastasis in Melatonin vs. Control arm, evaluated with the Log-rank test.

  5 years

• 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).

  5 years

• Number of patients that develop other cancers (i.e., cancer diagnoses other than uveal melanoma) in Melatonin vs. Control arm, evaluated as Cox regression hazard ratio (HR).

  5 years

Other Outcomes (2)

• Interim analysis: Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as relative risk (RR).

  3 years

• Interim analysis: Overall survival (OS) in Melatonin vs. Control arm, evaluated with the Log-rank test.

  3 years

Study Arms (2)

Melatonin

EXPERIMENTAL

Melatonin tablet 5 mg. 4 tablets taken at night (20 mg) for 5 years.

Drug: Melatonin

Control

NO INTERVENTION

No intervention. Follows the current standard of observation after primary tumor treatment.

Interventions

Melatonin DRUG

White 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.

Also known as: Melatonin AGB Pharma

Melatonin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• AND at least one of the following 7 items:
• 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.
• 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.
• The patient's tumor was of size category T2a before plaque brachytherapy and has then recurred.
• The patient's tumor has an epithelioid cell type (\>5 epithelioid cells per high power field and \>90 % of tumor cells epithelioid).
• The patient's tumor has a low immunohistochemical expression of BAP1.
• The patient's tumor has more than 9 mitoses per high power field.
• 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).
• If the patient is already being treated with Melatonin, a two-week wash out period will be applied before randomization.

You may not qualify if:

• 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)
• 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.
• 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.
• The patient has epilepsy.
• The primary UM was diagnosed more than 12 months ago.

Sponsors & Collaborators

• Gustav Stalhammar: lead
• Karolinska Trial Alliance: collaborator
• The Swedish Eye Foundation (Ögonfonden): collaborator
• The Swedish Society of Medicine: collaborator
• Swedish Cancer Foundation: collaborator

Study Sites (1)

St. Erik Eye Hospital

Stockholm, Stockholm County, 17164, Sweden

RECRUITING

Related Publications (2)

• Kal Omar R, Hagstrom A, Stalhammar G. Adjuvant melatonin for uveal melanoma (AMUM): protocol for a randomized open-label phase III study. Trials. 2023 Mar 26;24(1):230. doi: 10.1186/s13063-023-07245-9.

  PMID: 36966349 BACKGROUND

• Hagstrom A, Kal Omar R, Williams PA, Stalhammar G. The rationale for treating uveal melanoma with adjuvant melatonin: a review of the literature. BMC Cancer. 2022 Apr 13;22(1):398. doi: 10.1186/s12885-022-09464-w.

  PMID: 35413810 BACKGROUND

Related Links

• Adjuvant melatonin for uveal melanoma (AMUM): protocol for a randomized open-label phase III study

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Gustav Stålhammar, MD PhD

  St. Erik Eye Hospital and Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gustav Stålhammar, MD PhD

CONTACT

0046812323000; gustav.stalhammar@ki.se

Anna Hagström, MD

CONTACT

amumstudien@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: M.D. Ph.D.

Model Details: 100 patients will be randomized into either adjuvant treatment with Melatonin or to a control group that will undergo standard follow-up with radiological examinations but no adjuvant treatment.

Study Record Dates

• First Submitted: August 11, 2022
• First Posted: August 16, 2022
• Study Start: October 2, 2022
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2031
• Last Updated: May 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)