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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Stage Cancer
• Intervention / Treatment: Drug: Matched placebo; Drug: 10 mg Melatonin; Drug: 20 mg Melatonin

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
  • Khon Kaen, Thailand, 40000
    • Khon Kaen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Khon Kaen University
• Collaborators: Thailand Research Fund; Srinagarind Hospital, Khon Kaen University; Khon Kaen Hospital, Khon Kaen; General Drugs House Co.,LTD.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: October 11, 2012
• First Submitted That Met QC Criteria: October 11, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Estimate): October 15, 2012
• Last Update Submitted That Met QC Criteria: October 11, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: adjuvant therapy; melatonin; quality of life; cancer; survival; adverse events; oxidative stress
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: MIRCIT; TRF (Thailand Research Fund)