Comparison of Melatonin or Metformin and Dacarbazine Combination Versus Dacarbazine Alone in Disseminated Melanoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Multicenter Randomized Study to Compare Dacarbazine With Melatonin or Metformin Versus Dacarbazine in the First Line Therapy of Disseminated Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: Metformin
* Drug: Melatonin
* Drug: Dacarbazine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18. Obtained Inform Consent Morphologically confirmed disseminated Stage IV melanoma Eastern Collaborative Oncology Group Performance Status Scale 0 - 2. Expected survival >3 month Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dacarbazine with Metformin<br>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Metformin 850 mg BID. | Drug: Metformin<br>* per os 850 mg BID<br>* Other names: Siofor® 850;Drug: Dacarbazine<br>* IV 1 hour 1000 mg/m^2 once in 28 days<br>* Other names: DTIC;|
| Experimental: Dacarbazine and Melatonin<br>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days with Melatonin 3 mg before sleep daily. | Drug: Melatonin<br>* per os 3 mg daily<br>* Other names: Melaxen;Drug: Dacarbazine<br>* IV 1 hour 1000 mg/m^2 once in 28 days<br>* Other names: DTIC;|
| Active Comparator: Dacarbazine<br>32 patients will receive Dacarbazine 1000 mg/m^2 once every 28 days | Drug: Dacarbazine<br>* IV 1 hour 1000 mg/m^2 once in 28 days<br>* Other names: DTIC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 23 months after FPFV | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events (AE) incidence | Incidence of AE classified using NCI Common Terminology Criteria for AE v4 | 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. | 23 months after FPFV | 
| Immune system assessment | Following tests will be performed at baseline and each response assessment: Lymphocyte subpopulations detection Immunosuppressive factors measurements | 23 months after FPFV | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Melanoma, Melatonin, Metformin, Dacarbazine