Clinical trial NCT02332928: Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy
Official title: Melatonin Supplementation for Cancer-related Fatigue in Patients Receiving Radiotherapy: A Double Blind Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Breast Cancer - Female
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2015-01-07
Enrollment: 80
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Detailed description: Subjects will be randomized to receive either melatonin or placebo. 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. Patients with localized breast cancer will receive standard-of-care RT as determined by the treating physician. The RT regimens include: (1) 1 week of accelerated (APBI); (2) 3-4 weeks of an accelerated hypofractionation RT schedule; and (3) 6-8 weeks of a standard RT schedule. No additional concomitant medication or supportive care guidelines are required for this study. Subjects will receive daily melatonin or placebo beginning the night before their course of RT and for an additional 2-week period that extends beyond the conclusion of their RT. Subjects will be given a Study Diary to record their use of study medication. Patients will be followed for 60 days after removal from the study treatment or until death, whichever occurs first. Patients removed from the study treatment for unacceptable adverse events (AEs) will be followed until resolution or stabilization of the adverse event.

Eligibility criteria: Inclusion Criteria

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

Exclusion Criteria

1. 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
2. Patients with a creatinine clearance \<30 mL/min
3. Aspartate aminotransferase (AST) \> 3X upper limit of normal (ULN)
4. Alanine aminotransferase (ALT) \> 3X ULN
5. Bilirubin \> 1X ULN
6. Use of systemic steroids, or other pharmacological agents such as methylphenidate for cancer-related fatigue
7. Current use of American ginseng, remelteon, or warfarin.
8. Depression ≥ grade 2 (CTCAE v4.0)

Primary outcomes:
measure: Comparison of FACIT-Fatigue Subscale
timeFrame: Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)
Secondary outcomes:
measure: 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.
timeFrame: Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)
measure: 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.
timeFrame: Baseline (Day 1) and 8 weeks post RT (variable, approximately 64 weeks)
measure: Comparison of Edmonton Symptom Assessment System (ESAS) Scores Obtained at Baseline Until Completion of RT.
timeFrame: Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)
measure: Comparison of the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short Form 8a Scores Obtained at Baseline and at the Completion of RT.
timeFrame: Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)
measure: Determine the Level of Agreement in Reported Fatigue Scores When 2 Different Survey Instruments Are Used to Measure Fatigue.
timeFrame: Baseline,( Day 1), 2 weeks post radiation therapy completion (variable, approximately 58 weeks)
measure: Compare the Number of Hospital Admissions, Emergency Center Visits, and Medical Days Off Work Between Patients Receiving Melatonin Compared to Placebo.
timeFrame: Baseline (day 1) to 8 weeks post RT (variable, approximately 64 weeks)
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University/Massey Cancer Center
state: Virginia
Study officials:
affiliation: Massey Cancer Center
name: Alfredo I Urdaneta, MD
role: PRINCIPAL_INVESTIGATOR
References: