Uveal MelanomaPhase 3AMUMNCT05502900
Adjuvant Melatonin for Uveal Melanoma
A Phase 3 study testing Melatonin in people with Uveal Melanoma and Uveal Melanoma, Posterior, Medium/Large Size, run by Gustav Stalhammar at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma, Uveal Melanoma, Posterior, Medium/Large Size, Eye Cancer, Intraocular Melanoma
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteSweden
- Study dates
- 2 Oct 2022to 1 Jan 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- The patient has epilepsy.
- 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.
- The primary UM was diagnosed more than 12 months ago.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Anna Hagström, MD contact
Sweden1 site, 1 recruiting
- Recruiting
St. Erik Eye Hospital
Stockholm, Stockholm County, 17164
Gustav Stålhammar, MD PhD, 0046812323000
Anna Hagström, MD
About this study
Official title: Adjuvant Melatonin for Uveal Melanoma: A Randomized Open Phase III Study
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).
Read the detailed description
At the time of primary UM diagnosis, about 2 % of patients have radiologically detectable metastases. Within 15 years, this proportion increases to 32-45 % even with successful treatment of the eye. Presumably, this is caused by subclinical dormant micrometastases that most frequently locate to the liver. Once these leave their dormant state and grow into clinically detectable lesions, few effective treatment alternatives are available and the median patient survival is about one year.
Several trials have tested interventions for metastatic UM, and in comparison with the greatly improved results for cutaneous melanoma during the last decades, response rates and durations have been low.
The AMUM trial will therefore test if adjuvant treatment with Melatonin for 5 years after primary tumor diagnosis can prevent or delay the onset of metastases. 100 patients recently diagnosed with primary UM and found to have a high risk of metastasis will be recruited. The trial is administered from St. Erik Eye Hospital, Stockholm, Sweden, who has a national responsibility for the diagnosis, plaque brachytherapy treatment and histopathological examination of uveal melanomas. This means that all Swedish patients that are diagnosed with uveal melanoma may be considered for inclusion in the trial, regardless of their region of residence. Patients will be screened for eligibility, informed, recruited, randomized, and treated from St. Erik Eye Hospital. Follow-up will be conducted in cooperation with multiple centers all over the country.
When informed consent has been obtained, the 100 patients will then be randomized to either treatment with oral tablets of Melatonin (20 mg, taken before bedtime) for 5 years, or to a control group. Both groups will be followed with regular contacts from the investigators, with radiological examinations of the liver every 6 months, and with a blood test at the time of recruitment and then year 2 and 4.
When the last patient has taken his or her last tablet after 5 years of treatment, we will examine the primary outcome measure (relative risk of metastasis) and secondary outcome measures (overall survival, survival after development of metastases, number of patients developing other cancers, adverse events (AE) and serious adverse events (SAE)) in the Melatonin vs. control arm.
AMUM is an Investigator-Initiated Trial without commercial interests.
- Conditions
- Uveal Melanoma, Uveal Melanoma, Posterior, Medium/Large Size, Eye Cancer, Intraocular Melanoma
- Being tested
- Melatonin
- Keywords
- Melatonin, Adjuvant, Preventive, Uveal melanoma, Survival, Phase 3 trial
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called Melatonin AGB Pharma
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.
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Melatonin tablet 5 mg. 4 tablets taken at night (20 mg) for 5 years. Receives: Drug: Melatonin |
| Control | No intervention | No intervention. Follows the current standard of observation after primary tumor treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 5 years
Secondary outcomes (6)
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.
Measured: 5 years
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.
Measured: 5 years
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.
Measured: 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).
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.
Measured: 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).
Measured as hazard ratio (i.e., the hazard for other cancers 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.
Measured: 5 years
Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) in Melatonin vs. Control arm, as assessed by CTCAE v5.0.
Frequency of adverse events (AEs) and serious adverse events (SAEs) in the Melatonin vs. Control arm, evaluated as relative risk (RR) with 95 % confidence interval.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2022
- Study start2 Oct 2022
- Primary completion1 Jan 2031 (estimated)
- Study completion1 Jan 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Gustav Stalhammar
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Trial Alliance, The Swedish Eye Foundation (Ögonfonden), The Swedish Society of Medicine, Swedish Cancer Foundation
- Responsible party
- Sponsor-investigator, Gustav Stalhammar, St. Erik Eye Hospital
- Investigators
- Gustav Stålhammar, MD PhD, Principal investigator, St. Erik Eye Hospital and Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05502900
- Sponsor's protocol ID
- AMUM v 2.0
- Other IDs
- 2022-500307-49
- Acronym
- AMUM
- Status last verified
- May 2025
- First submitted
- 11 Aug 2022
- Last updated
- 15 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36966349Hagstrom 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.
PubMed 35413810
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjuvant Melatonin for Uveal Melanoma: A Randomized Open Phase III Study
- ClinicalTrials.gov ID
- NCT05502900
- Acronym / sponsor ID
- AMUM / AMUM v 2.0
- Conditions
- Uveal Melanoma, Uveal Melanoma, Posterior, Medium/Large Size, Eye Cancer, Intraocular Melanoma
- Keywords
- Melatonin, Adjuvant, Preventive, Uveal melanoma, Survival, Phase 3 trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Gustav StalhammarUniversity, hospital or other
- Collaborators
- Karolinska Trial Alliance, The Swedish Eye Foundation (Ögonfonden), The Swedish Society of Medicine, Swedish Cancer Foundation
- Study start
- 2 Oct 2022 (actual)
- Primary completion
- 1 Jan 2031 (estimated)
- Study completion
- 1 Jan 2031 (estimated)
- First posted
- 16 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
At the time of primary UM diagnosis, about 2 % of patients have radiologically detectable metastases. Within 15 years, this proportion increases to 32-45 % even with successful treatment of the eye. Presumably, this is caused by subclinical dormant micrometastases that most frequently locate to the liver. Once these leave their dormant state and grow into clinically detectable lesions, few effective treatment alternatives are available and the median patient survival is about one year.
Several trials have tested interventions for metastatic UM, and in comparison with the greatly improved results for cutaneous melanoma during the last decades, response rates and durations have been low.
The AMUM trial will therefore test if adjuvant treatment with Melatonin for 5 years after primary tumor diagnosis can prevent or delay the onset of metastases. 100 patients recently diagnosed with primary UM and found to have a high risk of metastasis will be recruited. The trial is administered from St. Erik Eye Hospital, Stockholm, Sweden, who has a national responsibility for the diagnosis, plaque brachytherapy treatment and histopathological examination of uveal melanomas. This means that all Swedish patients that are diagnosed with uveal melanoma may be considered for inclusion in the trial, regardless of their region of residence. Patients will be screened for eligibility, informed, recruited, randomized, and treated from St. Erik Eye Hospital. Follow-up will be conducted in cooperation with multiple centers all over the country.
When informed consent has been obtained, the 100 patients will then be randomized to either treatment with oral tablets of Melatonin (20 mg, taken before bedtime) for 5 years, or to a control group. Both groups will be followed with regular contacts from the investigators, with radiological examinations of the liver every 6 months, and with a blood test at the time of recruitment and then year 2 and 4.
When the last patient has taken his or her last tablet after 5 years of treatment, we will examine the primary outcome measure (relative risk of metastasis) and secondary outcome measures (overall survival, survival after development of metastases, number of patients developing other cancers, adverse events (AE) and serious adverse events (SAE)) in the Melatonin vs. control arm.
AMUM is an Investigator-Initiated Trial without commercial interests.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: MelatoninMelatonin tablet 5 mg. 4 tablets taken at night (20 mg) for 5 years. |
| Control | No intervention | –No intervention. Follows the current standard of observation after primary tumor treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninAlso: Melatonin AGB PharmaWhite 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. | Drug | Melatonin |
Primary outcome
Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as relative risk (RR).
Time frame: 5 years
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.
6 secondary outcomes
Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as Cox regression hazard ratio (HR).
Time frame: 5 years
Overall survival (OS) time from randomization in Melatonin vs. Control arm, evaluated with the Log-rank test.
Time frame: 5 years
Overall survival (OS) time from the detection of metastasis in Melatonin vs. Control arm, evaluated with the Log-rank test.
Time frame: 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).
Time frame: 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).
Time frame: 5 years
Number of participants with treatment-related adverse events (AEs) and serious adverse events (SAEs) in Melatonin vs. Control arm, as assessed by CTCAE v5.0.
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2025.
- Background: PubMed 36966349Kal 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.
- Background: PubMed 35413810Hagstrom 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.
- Adjuvant melatonin for uveal melanoma (AMUM): protocol for a randomized open-label phase III studyLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Anna Hagström, MD contact
Gustav Stålhammar, MD PhD principal investigator
St. Erik Eye Hospital and Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melatonin in people with Uveal Melanoma and Uveal Melanoma, Posterior, Medium/Large Size, run by Gustav Stalhammar at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gustav Stålhammar, MD PhD (0046812323000, gustav.stalhammar@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients that develop metastases in Melatonin vs. Control arm, evaluated as relative risk (RR). (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05502900, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2025.