MelanomaPhase 2NCT02190838
Comparison of Melatonin or Metformin and Dacarbazine Combination Versus Dacarbazine Alone in Disseminated Melanoma
A Phase 2 study testing Metformin, Melatonin and Dacarbazine in people with Melanoma, run by N.N. Petrov National Medical Research Center of Oncology at 3 sites in Russia.
Trial summary
Treatment of disseminated melanoma is still a difficult issue. Obvious achievements of recent years proves efficacy of immunologic approachees in this field. The ability of melatonin and metformin to decrease metabolic immunosuppression was shown in many experimental studies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Metformin, Melatonin and Dacarbazine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 3 sitesRussia
- Study dates
- Apr 2014to 31 Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- Age >18.
- Obtained Inform Consent
- Morphologically confirmed disseminated Stage IV melanoma
- Eastern Collaborative Oncology Group Performance Status Scale 0 - 2.
- Expected survival >3 month
Who cannot join
- Evidence of active brain lesions (brain lesions after stereotaxic ray therapy allowed)
- Evidence of liver and bone marrow clinically meaningful disfunction
- Severe uncontrolled concomitant conditions and diseases
- Pregnancy or lactation
- Systemic therapy for disseminated melanoma
- Second malignancy
- Diabetes mellitus requiring drug therapy
- Any condition preventing study participation by investigator opinion
Trial locations and contacts
3 sites in 1 country.
Russia3 sites
N.N. Petrov Research Institute of Oncology Clinical Diagnostic Department
Saint Petersburg, 191124
N.N. Petrov Research Institute of Oncology Ambulatory Chemotherapy Department
Saint Petersburg, 197758
N.N. Petrov Research Institute of Oncology Chemotherapy and Innovative Technologies Department
Saint Petersburg, 197758
About this study
Official title: Phase II Multicenter Randomized Study to Compare Dacarbazine With Melatonin or Metformin Versus Dacarbazine in the First Line Therapy of Disseminated Melanoma
Treatment of disseminated melanoma is still a difficult issue. Obvious achievements of recent years proves efficacy of immunologic approachees in this field. The ability of melatonin and metformin to decrease metabolic immunosuppression was shown in many experimental studies. Some literature data confirm the possibility of increasing efficacy of melatonin with dacarbazine (DTIC) and metformin with DTIC combinations. We hypothesized that this combinations could be more effective than DTIC monotherapy in terms of response rate and time to progression.
- Conditions
- Melanoma
- Keywords
- Melanoma, Melatonin, Metformin, Dacarbazine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Siofor® 850
per os 850 mg BID
MelatoninDrug
Also called Melaxen
per os 3 mg daily
DacarbazineDrug
Also called DTIC
IV 1 hour 1000 mg/m^2 once in 28 days
| Study group | Role | What they receive |
|---|---|---|
| Dacarbazine with Metformin | Experimental | 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Metformin 850 mg BID. Receives: Drug: Metformin; Drug: Dacarbazine |
| Dacarbazine and Melatonin | Experimental | 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Melatonin 3 mg before sleep daily. Receives: Drug: Melatonin; Drug: Dacarbazine |
| Dacarbazine | Active comparator | 32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days Receives: Drug: Dacarbazine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate
Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is defined as the proportion of patients with a best overall response of complete response or partial response
Measured: 23 months after FPFV
Progression Free Survival
As per RECIST v1.1. progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.
Measured: 23 months after FPFV
Secondary outcomes (3)
Adverse events (AE) incidence
Incidence of AE classified using NCI Common Terminology Criteria for AE v4
Measured: until 30 days after last patient treatment visit
Metabolic Changes Incidence
Nutritional status will be assessed using Nutritional Risk Index (NRI), Subjective global assessment (SGA), and Body Mass Index (BMI) tools.
Measured: 23 months after FPFV
Immune system assessment
Following tests will be performed at baseline and each response assessment:
- Lymphocyte subpopulations detection
- Immunosuppressive factors measurements
Measured: 23 months after FPFV
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2014 (estimated)
- Study startApr 2014
- Primary completion12 Dec 2015
- Study completion31 Dec 2018
Why it stopped: Preliminary terminated due to inefficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- N.N. Petrov National Medical Research Center of Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Aleksei V. Novik, MD, PhD, Principal investigator, N.N. Petrov Research Institute of OncologyIrina A. Baldueva, MD, PhD, DSc, Study director, N.N. Petrov Research Institute of Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02190838
- Sponsor's protocol ID
- MMM-1
- Status last verified
- Sep 2019
- First submitted
- 13 Jul 2014
- Last updated
- 25 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Novik AV, Protsenko SA, Baldueva IA, Berstein LM, Anisimov VN, Zhuk IN, Semenova AI, Latipova DK, Tkachenko EV, Semiglazova TY. Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma. Oncologist. 2021 May;26(5):364-e734. doi: 10.1002/onco.13761. Epub 2021 Apr 9.
PubMed 33749049
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Multicenter Randomized Study to Compare Dacarbazine With Melatonin or Metformin Versus Dacarbazine in the First Line Therapy of Disseminated Melanoma
- ClinicalTrials.gov ID
- NCT02190838
- Acronym / sponsor ID
- MMM-1
- Conditions
- Melanoma
- Keywords
- Melanoma, Melatonin, Metformin, Dacarbazine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Preliminary terminated due to inefficacy
- Enrolment
- 57 participants (actual)
- Lead sponsor
- N.N. Petrov National Medical Research Center of OncologyUniversity, hospital or other
- Study start
- Apr 2014 (actual)
- Primary completion
- 12 Dec 2015 (actual)
- Study completion
- 31 Dec 2018 (actual)
- First posted
- 15 Jul 2014 (estimated)
- 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.
Treatment of disseminated melanoma is still a difficult issue. Obvious achievements of recent years proves efficacy of immunologic approachees in this field. The ability of melatonin and metformin to decrease metabolic immunosuppression was shown in many experimental studies. Some literature data confirm the possibility of increasing efficacy of melatonin with dacarbazine (DTIC) and metformin with DTIC combinations. We hypothesized that this combinations could be more effective than DTIC monotherapy in terms of response rate and time to progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dacarbazine with Metformin | Experimental | Drug: Metformin, Drug: Dacarbazine32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Metformin 850 mg BID. |
| Dacarbazine and Melatonin | Experimental | Drug: Melatonin, Drug: Dacarbazine32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Melatonin 3 mg before sleep daily. |
| Dacarbazine | Active comparator | Drug: Dacarbazine32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age >18.
- Obtained Inform Consent
- Morphologically confirmed disseminated Stage IV melanoma
- Eastern Collaborative Oncology Group Performance Status Scale 0 - 2.
- Expected survival >3 month
Key exclusion criteria (8 listed)
- Evidence of active brain lesions (brain lesions after stereotaxic ray therapy allowed)
- Evidence of liver and bone marrow clinically meaningful disfunction
- Severe uncontrolled concomitant conditions and diseases
- Pregnancy or lactation
- Systemic therapy for disseminated melanoma
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 |
|---|---|---|
| MetforminAlso: Siofor® 850per os 850 mg BID | Drug | Dacarbazine with Metformin |
| MelatoninAlso: Melaxenper os 3 mg daily | Drug | Dacarbazine and Melatonin |
| DacarbazineAlso: DTICIV 1 hour 1000 mg/m^2 once in 28 days | Drug | Dacarbazine, Dacarbazine and Melatonin, Dacarbazine with Metformin |
Primary outcome
Response Rate
Time frame: 23 months after FPFV
Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. ORR is defined as the proportion of patients with a best overall response of complete response or partial response
Progression Free Survival
Time frame: 23 months after FPFV
As per RECIST v1.1. progression-free survival (PFS) is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.
3 secondary outcomes
Adverse events (AE) incidence
Time frame: until 30 days after last patient treatment visit
Metabolic Changes Incidence
Time frame: 23 months after FPFV
Immune system assessment
Time frame: 23 months after FPFV
Results and safety
The study was stopped early (reason given: Preliminary terminated due to inefficacy). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2019.
- Derived from this study: PubMed 33749049Novik AV, Protsenko SA, Baldueva IA, Berstein LM, Anisimov VN, Zhuk IN, Semenova AI, Latipova DK, Tkachenko EV, Semiglazova TY. Melatonin and Metformin Failed to Modify the Effect of Dacarbazine in Melanoma. Oncologist. 2021 May;26(5):364-e734. doi: 10.1002/onco.13761. Epub 2021 Apr 9.
- 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. This study is not recruiting at the moment.
Aleksei V. Novik, MD, PhD principal investigator
N.N. Petrov Research Institute of Oncology
Irina A. Baldueva, MD, PhD, DSc study director
N.N. Petrov Research Institute of Oncology
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin, Melatonin and Dacarbazine in people with Melanoma, run by N.N. Petrov National Medical Research Center of Oncology at 3 sites in Russia.
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 5 inclusion and 8 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: stopped early, as of the sponsor's last update on 25 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Russia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Preliminary terminated due to inefficacy). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response Rate (time frame: 23 months after FPFV). The study lists 2 primary outcomes in all. 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 NCT02190838, which also lists 1 linked publication.
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 25 Nov 2019.