Trial Title:
Adjuvant Melatonin for Uveal Melanoma
NCT ID:
NCT05502900
Condition:
Uveal Melanoma
Uveal Melanoma, Posterior, Medium/Large Size
Eye Cancer, Intraocular Melanoma
Conditions: Official terms:
Melanoma
Uveal Neoplasms
Eye Neoplasms
Melatonin
Conditions: Keywords:
Melatonin
Adjuvant
Preventive
Uveal melanoma
Survival
Phase 3 trial
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention 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.
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Melatonin
Description:
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.
Arm group label:
Melatonin
Other name:
Melatonin AGB Pharma
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).
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
St. Erik Eye Hospital
Address:
City:
Stockholm
Zip:
17164
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Gustav Stålhammar, MD PhD
Phone:
0046812323000
Investigator:
Last name:
Anna Hagström, MD
Email:
Sub-Investigator
Investigator:
Last name:
Ruba Kal-Omar, MD
Email:
Sub-Investigator
Start date:
October 2, 2022
Completion date:
January 1, 2031
Lead sponsor:
Agency:
Gustav Stalhammar
Agency class:
Other
Collaborator:
Agency:
Karolinska Trial Alliance
Agency class:
Industry
Collaborator:
Agency:
Swedish Cancer Society
Agency class:
Other
Collaborator:
Agency:
The Swedish Eye Foundation (Ögonfonden)
Agency class:
Other
Collaborator:
Agency:
The Swedish Society of Medicine
Agency class:
Other
Source:
St. Erik Eye Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05502900
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-022-09464-w
