Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy

NCT02332928 | Terminated Phase 3 Results DMC FDA Drug

• 4 other identifiers: MCC-12-08248HM20003275NCI-2015-00345P30CA016059
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, placebo-controlled trial wherein subjects with breast cancer will be randomized to receive either 20 mg oral melatonin or placebo the night before their first radiotherapy (RT), nightly throughout their RT, and for an additional 2 weeks following the completion of their RT. After informed consent is obtained from eligible subjects, they will then be electronically randomized on a 1:1 ratio to melatonin treatment or placebo. The subjects will be stratified according to treatment duration (less than 3 weeks; equal to or greater than 3 weeks) and prior chemotherapy.

Conditions

Breast Cancer - Female

Outcome Measures

Primary Outcomes (1)

• Comparison of FACIT-Fatigue Subscale

  Determine if the average increase in fatigue (as measured by the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue subscale) from baseline to completion of RT is different in those patients who received melatonin than in those who received placebo. The FACIT-F is a well-validated QOL instrument widely used for the assessment of cancer-related fatigue in clinical trials. It consists of 27 general QOL questions divided into 4 domains (physical, social, emotional, and functional), plus a 13-item fatigue sub-score. The patient rates the intensity of fatigue and its related symptoms on a scale of 0-4. The total score ranges between 0 and 52, with higher scores denoting less fatigue.

  Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)

Secondary Outcomes (6)

• Comparison of Functional Assessment of Chronic Illness Therapy (FACIT-F) Scores in Fatigue From Baseline Until 2 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.

  Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)

• Comparison in Functional Assessment of Chronic Illness Therapy (FACIT) in Fatigue From Baseline Until 8 Weeks After Completion of RT in Those Patients Who Received Melatonin Compared to Those Who Received Placebo.

  Baseline (Day 1) and 8 weeks post RT (variable, approximately 64 weeks)

• Comparison of Edmonton Symptom Assessment System (ESAS) Scores Obtained at Baseline Until Completion of RT.

  Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)

• Comparison of the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a Scores Obtained at Baseline and at the Completion of RT.

  Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)

• Determine the Level of Agreement in Reported Fatigue Scores When 2 Different Survey Instruments Are Used to Measure Fatigue.

  Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)

Study Arms (2)

20 mg Melatonin

ACTIVE COMPARATOR

RT (as clinically indicated) + melatonin (Subjects will receive 20-mg oral melatonin the night before their first RT treatment, each night throughout the course of RT treatment, and for 2 weeks following the completion of RT).

Drug: Melatonin

Placebo

PLACEBO COMPARATOR

RT (as clinically indicated) + placebo (Subjects will receive 20-mg oral placebo the night before their first RT treatment, each night throughout the course of RT treatment, and for 2 weeks following the completion of RT).

Drug: Placebo

Interventions

Melatonin DRUG

Melatonin + RT (as clinically indicated) (Subjects will receive 20-mg oral melatonin or placebo the night before their first RT treatment, each night throughout the course of RT treatment, and for 2 weeks following the completion of RT).

20 mg Melatonin

Placebo DRUG

Placebo + RT (as clinically indicated) (Subjects will receive 20-mg oral melatonin or placebo the night before their first RT treatment, each night throughout the course of RT treatment, and for 2 weeks following the completion of RT).

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ambulatory outpatients with breast (including ductal carcinoma in situ \[DCIS\]) cancer.
• Patients to be treated with RT for curative intent.
• Women ≥18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status \<3 (Appendix 4).
• Hemoglobin ≥ 9 g/dL
• Either post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control during study treatment and for 3 months afterwards.
• Subjects who are currently taking melatonin must discontinue melatonin for 5 days before enrolling in the study.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Fatigue brought on by conditions other than cancer such as (the indicated tests are required only if that mechanism of fatigue is suspected):
• uncontrolled hypothyroidism (TSH \>10 IU)
• hypercalcemia (calcium \>11 mg/dL) Calcium (Ca) = Serum Calcium (SerumCa) + 0.8 \* (NormalAlbumin - PatientAlbumin)
• decompensated congestive heart failure
• chronic obstructive pulmonary disease requiring oxygen replacement
• Patients with a creatinine clearance \<30 mL/min
• Aspartate aminotransferase (AST) \> 3X upper limit of normal (ULN)
• Alanine aminotransferase (ALT) \> 3X ULN
• Bilirubin \> 1X ULN
• Use of systemic steroids, or other pharmacological agents such as methylphenidate for cancer-related fatigue
• Current use of American ginseng, remelteon, or warfarin.
• Depression ≥ grade 2 (CTCAE v4.0)

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

The study had an initial goal of 142 patients, with interim analysis at half recruitment. Upon recommendation from the Data and Safety Monitoring Committee (DSMC), the study concluded at interim analysis due to lack of efficacy.

Results Point of Contact

• Title: Massey Cancer Center Cancer Prevention & Control Team
• Organization: Virginia Commonwealth University Massey Cancer Center

masseycpc@vcu.edu

877-462-7739

Study Officials

• Alfredo I Urdaneta, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2014
• First Posted: January 7, 2015
• Study Start: March 25, 2015
• Primary Completion: June 2, 2021
• Study Completion: June 2, 2021
• Last Updated: March 30, 2023
• Results First Posted: March 30, 2023

Record last verified: 2023-03

Locations

US (1)