Symptoms and General Pathology

All Conditions

Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

Recurrence

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Disease Attributes

Central Nervous System Depressants

All Drugs and Chemicals

Other Dietary Supplements

Melatonin

Antioxidants

Protective Agents

To receive 20 mg of melatonin nightly for 1 year post-surgery

To receive 20 mg placebo nightly for 1 year post-surgery

melatonin

similar to experimental in all ways except for lack of active ingredient

placebo

Dugald MR Seely, ND, MSc

Andrew JE Seely, MD

There is evidence to support the use of melatonin, a natural health product, as an additional treatment aid for cancer patients. This study is designed to see if the daily ingestion of 20 milligrams of melatonin for one year can lower the incidence of developing lung cancer recurrence and/or death. Only patients with a diagnosis of non small cell lung cancer who are eligible for surgical resection can participate in the trial. The study will also be assessing for changes in quality of life, pain, fatigue, anxiety, sleep, and depression amongst the participants.

The trial employs a two-armed parallel placebo controlled trial design whereby patients with a diagnosis of non small cell lung cancer are randomized to receive either 20 mg of melatonin nightly or an identically matched placebo. All patients will be followed for two years with primary outcomes assessed at a two year time point and secondary outcomes evaluated throughout the course of the trial.

Adjuvant Melatonin for Prevention of Lung Cancer Recurrence and Mortality

Adjuvant Melatonin for Prevention of Lung Cancer Recurrence and Mortality: A Randomized Placebo Controlled Clinical Trial

Disease-Free survival (DFS) at 2 years post-surgery. DFS is measured by the number of participants in both arms who have experienced a recurrence OR mortality at 2 years.

Participant-reported quality of life using the European Organization for Research and Treatment of Cancer's Quality of Life Questionnaire C-30 (EORTC QLQ C-30) and Lung Cancer 13 (EORTC QLQ LC13) questionnaires. Scores represent a value from 0-100. Symptom and LC13 scale: 0 represents best health, 100 worst health. Global and functional scales: 100 represents best health, 0 represents worst health. Full scoring algorithms available here: https://www.eortc.org/app/uploads/sites/2/2018/02/SCmanual.pdf

Measured using the Multidimensional Fatigue Inventory 20 (MFI-20) questionnaire. Scores are on a scale of 0-100, where 100 is the best health and 0 is the worst health.

Measured using the Medical Outcomes Study (MOS) Sleep Survey. Scales used were Sleep Adequacy and Sleep problems Index II. Scores are on a scale of 0-100. Sleep Adequacy: 100 represents best health; 0 represents worst health. Problems index: 0 represents best health; 100 represents worst health.

Calculated using the Brief Pain Inventory. Each scale ranges from 0-10, where 0 is no pain and 10 is the worst possible pain.

Measured using the Beck Anxiety Inventory. Scored range from 0-63, where 0 is no anxiety and 63 is the worst possible anxiety.

Measured using the Beck Depression Inventory II. Scores range from 0-63, where 0 is no depression and 63 is the worst possible depression.

Number of participants who experienced an adverse event related to their adjuvant chemotherapy

Measured as disease-free survival (DFS) at 5 years. DFS was measured by the incidence of a recurrence OR mortality up to 5 years post-surgery.

NK cell cytotoxicity changes from baseline to 6 months

Number of participants who experienced an adverse event related to their adjuvant radiation therapy

Differences in NK cell cytotoxicity between both arms

The Ottawa Hospital

Lotte & John Hecht Memorial Foundation

Gateway for Cancer Research

The Canadian College of Naturopathic Medicine

An adverse event is any untoward medical occurrence in a patient administered a medicinal product which does not necessarily have to have a causal relationship with this treatment. A serious adverse event is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or results in prolonging of existing hospitalization, results in a persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.

To receive 20 mg placebo nightly for 1 year post-surgery

placebo: similar to experimental in all ways except for lack of active ingredient

Placebo

To receive 20 mg of melatonin nightly for 1 year

melatonin: 20 mgs ingested nightly

Treatment

To receive matched supplement to the experimental arm in same schedule

placebo: similar to experimental in all ways except for lack of active ingredient

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Pre-Operative Chemotherapy or Radiation

Current Smoker

Past Smoker

Never Smoked

Unknown

Smoking History

Squamous Cell

Adenocarcinoma

Large Cell

Bronchoalveolar

Undifferentiated

Other

Non-Surgical

Histological Subtype

Minimally Invasive Surgery (MIS)

MIS Converted to Open

Open

Incision Type

Pneumonectomy

Lobectomy

Segmentectomy

Wedge Resection

No Operation

Surgery Type

Stage I

Stage II

Stage III

Stage IV

Overall 7th Edition American Joint Committee on Cancer (AJCC) stage (I-IV) based on the TNM classification. T refers to tumor size, N refers to nearby lymph nodes and M represents metastasized (spread) to other parts of the body. This staging number is obtained as a sum of the TNM classification. The lower the number, the lower the cancer stage and the better the prognosis for the patient. The higher the stage, the worse the prognosis.

Pathological Cancer Stage

Mark Legacy, Clinical Trial Coordinator

Analysis conducted was an adjusted logistic regression (adjuvant chemotherapy, adjuvant radiation, smoking history). Results were presented as a relative risk. Based on an estimated 30% outcome rate of recurrence or mortality in the control arm, 294 participants per arm provided 80% power to detect a relative risk of one third at an alpha of 0.05. We inflated this sample size to 346 per arm to account for 15% lost to follow-up.

To receive 20 mg of melatonin nightly for 1 year following surgery.

To receive 20 mg placebo nightly for 1 year following surgery

placebo: similar to experimental in all ways except for lack of active ingredient

Intention to treat - all participants analyzed.

Lung Cancer Recurrence or Mortality - 2 Years

Symptom Scale (Baseline)

Symptom Scale (1Y)

Symptom Scale (2Y)

Functional Scale (Baseline)

Functional Scale (1Y)

Functional Scale (2Y)

Global Scale (Baseline)

Global Scale (1Y)

Global Scale (2Y)

LC13 Scale (Baseline)

LC13 Scale (1Y)

LC13 Scale (2Y)

To receive 20 mg of melatonin nightly for 1 year post surgery

To receive 20 mg placebo nightly for 1 year post surgery

placebo: similar to experimental in all ways except for lack of active ingredient

Quality of Life

Between-arm least squares mean difference in change from randomization to 24 months post-surgery represented the effect of the intervention.

Baseline

Fatigue

Sleep Adequacy (Baseline)

Sleep Adequacy (1Y)

Sleep Adequacy (2Y)

Sleep Problems Index II (baseline)

Sleep Problems Index II (1Y)

Sleep Problems Index II (2Y)

Sleep

3 months

Only those recruited from the Ottawa Hospital were included in this analysis.

Pain Levels

Only participants recruited from The Ottawa Hospital were included in the analysis.

Anxiety

Depression

Only those who received adjuvant chemotherapy were included in this analysis.

Adverse Events (Chemotherapy)

DFS up to five years post-surgery was compared using Kaplan-Meier curves and the log rank test, followed by a hazard ratio calculated using the Cox proportional hazard model adjusting for adjuvant chemotherapy, adjuvant radiation, and smoking history.

This analysis included only those with stage I or II cancer (pathologic stage). DFS up to five years post-surgery was compared using Kaplan-Meier curves and the log rank test, followed by a hazard ratio calculated using the Cox proportional hazard model adjusting for adjuvant chemotherapy, adjuvant radiation, and smoking history.

This analysis included only those participants who had stage III or IV cancer (pathologic stage). DFS up to five years post-surgery was compared using Kaplan-Meier curves and the log rank test, followed by a hazard ratio calculated using the Cox proportional hazard model adjusting for adjuvant chemotherapy, adjuvant radiation, and smoking history.

All participants

Early Stage Cancer

Late Stage Cancer

To receive 20 mg of melatonin nightly for 1 year following surgery

Lung Cancer Recurrence or Mortality - 5 Years

Cytotoxicity (baseline)

Cytotoxicity (6 months)

Participants who qualified for the sub-study only.

Blood Tests to Examine the Effects of Melatonin on the Immune System (Raw Values)

Only those who received adjuvant radiation were included in this analysis.

Adverse Events (Radiation)

This analysis compares the mean ratios of 6 month cytotoxicity and baseline cytotoxicity between arms.

Only those who were enrolled in the sub study and qualified for analysis were included.

Blood Tests to Examine the Effects of Melatonin on the Immune System (Comparison Between Groups)

To receive 20 mg of melatonin nightly for 1 year

melatonin: 20 mg ingested nightly

Spots Global Cancer Trial Database for natural health product (nhp)