Melatonin In Reduction of Chemotherapy-Induced Toxicity (MIRCIT) Trial

Study Overview
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Brief Summary
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Meta-analysis of previous studies have shown that melatonin is a beneficial adjutant for reducing chemotherapy-induced toxicity; however no randomized, double-blind, placebo controlled trials have been conducted. This study evaluates the effect of melatonin in improving quality of life and reducing chemotherapy-induced toxicity in advanced cancer patients. This is a multi-center, randomized, double-blind, placebo controlled trial conducted in patients with histologically proven advanced non small cell lung, breast, head and neck or sarcoma cancer. Mixed-block randomization, stratified by center and treatment scheme is used to divide eligible patients into three groups: melatonin 20 mg, 10 mg or matched placebo. The patients are required to take the studied drugs at night (after 21.00 pm) on the first day of chemotherapy and continue daily for six months. Standard treatment is chemotherapy according to each center's standard protocol. Study endpoints are QOL (FACT), adverse event frequency (CTCAE), oxidative stress status, melatonin level, and survival.

Official Title
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Melatonin In Cancer Patients Receiving Chemotherapy: A Randomized, Double Blind, Placebo, Controlled Trial

Conditions
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Advanced Stage Cancer

Intervention / Treatment
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* Drug: 10 mg Melatonin
* Drug: 20 mg Melatonin
* Drug: Matched placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically proven advanced NSCLC, breast, head and neck, sarcoma cancer Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 platelet count ≥100,000 cells/mm3 white blood cell count ≥ 3,000 cell/mm3 hemoglobin ≥ 10 g/dL serum creatinine ≤ 1.5 mg/dL bilirubin ≤ 2 mg/dL AST ≤ 2.5 times upper limit of normal(ULN)for subjects without metastases or AST ≤ 2.5 times UNL for those with liver metastases New York Heart Association grade ≤ 2 written consent Exclusion Criteria: Patients who receive prior chemotherapy or biotherapy, radiotherapy or surgery within 1 month preceding randomization Patients who have more than one type of cancer or brain metastasis were excluded from the trial. Patients with moderate neuropathy (CTCAE grade ≥ 2) Patients with an active infection, or uncontrolled complications (i.e. blood glucose > 200 mg/dL, uncontrolled hypertension, unstable angina, history of congestive heart failure or history of myocardial infarction within one year).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Matched placebo<br>Matched placebo (identical formulation and delivery, without active ingredient) | Drug: Matched placebo<br>* Matched placebo (identical formulation and delivery, without active ingredient)<br>|
| Active Comparator: Drug: 10 mg Melatonin<br>10 mg melatonin gelatin capsule | Drug: 10 mg Melatonin<br>* Active Comparator: Drug: Melatonin 10 mg<br>|
| Active Comparator: Drug: 20 mg Melatonin<br>20 mg melatonin gelatin capsule | Drug: 20 mg Melatonin<br>* Active Comparator: Drug: Melatonin 20 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of Life (FACT) | Self-reported questionnaires. FACT-L, FACT-B, FACT-H&N and FACT-G Thai Version 4 has been previously validated. FACT-L, FACT-B, FACT-H&N and FACT-G are used in lung, breast, head&neck and sarcoma cancer patients, respectively. Change from baseline will be evaluated at 1,2,3 and 6 months after treatment. | Change from baseline in total scores at 6 months after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events | CTCAE Version 4.3 | Baseline and 1,2,3 and 6 months after treatment | 
| Oxidative stress status | 8-isoprostane and 8-hydroxydeoxyguanosine urine and MDA plasma analysis | Chemotherapy cycles 1,2,3,4 | 
| Melatonin level | Blood, urine and saliva analysis | Chemotherapy cycle 1,2,3 and 4 | 
| Overall survival | Overall survival | Over 4 years of the study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, melatonin, adjuvant therapy, quality of life, survival, adverse events, oxidative stress