Double-blind Randomized Controlled Trial Comparing Suvorexant 20 mg to Placebo for Treatment of Insomnia in Cancer Survivors

Cancer survivors have an incidence of sleep disturbance and insomnia higher than the general population, with significant potential implications on health outcomes including in survivorship domains and mortality outcomes. Available pharmacologic options for management of sleep disturbance are limited in efficacy and in their side effects. Investigators propose a double-blind placebo-controlled trial evaluating the use of the use of Suvorexant in breast cancer survivors on selective estrogen receptor modulators or aromatase inhibitors with sleep disturbance to assess the impact on insomnia symptoms and quality of life. Evaluation of breast cancer survivors on endocrine therapy uses a study population with high 5-year survival rate while retaining the capacity for recruitment and creating an opportunity to explore potential effects on vasomotor symptoms. Suvorexant has the potential to have a significant impact in cancer survivors not only on sleep related outcomes but also on cancer survivorship outcomes.

The purpose of the research study is to evaluate the ability of Suvorexant, a medication approved by the Food and Drug Administration (FDA) for insomnia, to treat sleep disturbance in breast cancer survivors on endocrine therapy.

• Suvorexant Tablets (Drug): Suvorexant initially with 10-20 mg for 28 days
• Placebo Control (Other): Matched Placebo Control for 28 days

Primary outcomes

• Participant Reported Insomnia Symptoms Evaluated Using the Insomnia Severity Index (ISI) [4 weeks]: The ISI is scored on a scale of 0-28 based on responses to 7 questions, with higher values indicating more severe symptoms of sleep disturbance. Five participants completed the study.

Secondary outcomes

• Vasomotor Symptoms Assessed Using the Hot Flash Related Daily Interference Scale [4 weeks]: Vasomotor symptoms were assessed using the Hot Flash Related Daily Interference Scale. This validated instrument measures the extent to which hot flashes interfere with daily activities and quality of life. Scores range from 0 to 100, with higher scores indicating greater interference due to vasomotor symptoms. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Quality of Life Evaluated Using the SF-36 [4 Weeks]: Health-related quality of life was assessed using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36). We have reported the average domain score for the general health domain. Each domain score ranges from 0 to 100, with higher scores indicating better health-related quality of life. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Quality of Life Evaluated Using the Cancer Problems in Living Scale (CPIL) [4 weeks]: Problems related to living with cancer were assessed using the Cancer Problems of Living (CPIL) Scale. The CPIL consists of a multi-item list of cancer-related problems across practical, emotional, and social domains. Participants rate each problem based on perceived severity, with higher ratings indicating greater problem severity. Each item is scored on a scale of 0-2 with the composite score reported. Score range from 0 to 58. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Pain Evaluation Evaluated Using the Brief Pain Inventory (BPI) [4 weeks]: Pain severity was assessed using the Brief Pain Inventory (BPI). The BPI asks participants to rate current pain, average pain, least pain, and worst pain on numeric rating scales ranging from 0 to 10, with higher scores indicating greater pain severity. A total pain severity score can be calculated by averaging these items. Score range is from 0 to 10. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Number of Participants Reported as Adherent Using the Simplified Medication Adherence Questionnaire (SMAQ) [4 weeks]: Medication adherence was assessed using the Simplified Medication Adherence Questionnaire (SMAQ). The SMAQ is a brief, participant-reported questionnaire composed of six multiple-choice questions evaluating medication-taking behavior. Non-adherence is indicated by any positive response suggesting missed doses or by reporting more than two missed doses during the preceding week. The outcome reported was the number of participants who were adherent based on this evaluation. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Vasomotor Symptoms Assessed Using the Hot Flash Related Daily Interference Scale [2 weeks]: Vasomotor symptoms were assessed using the Hot Flash Related Daily Interference Scale. This validated instrument measures the extent to which hot flashes interfere with daily activities and quality of life. Scores range from 0 to 100, with higher scores indicating greater interference due to vasomotor symptoms. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Participant Reported Insomnia Symptoms Evaluated Using the Insomnia Severity Index (ISI) [2 weeks]: The Insomnia Severity Index (ISI) score was evaluated at baseline, 2 weeks, and 4 weeks. The ISI is scored on a scale of 0-28 based on responses to 7 questions, with higher values indicating more severe symptoms of sleep disturbance. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.
• Pain Evaluation Evaluated Using the Brief Pain Inventory (BPI) [2 weeks]: Pain severity was assessed using the Brief Pain Inventory (BPI). The BPI asks participants to rate current pain, average pain, least pain, and worst pain on numeric rating scales ranging from 0 to 10, with higher scores indicating greater pain severity. A total pain severity score can be calculated by averaging these items. Score range is from 0 to 10. Five participants completed the study. Due to early study termination for insufficient accrual, the planned statistical analyses were not performed.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Adult post menopausal breast cancer survivors (female, > 18 years old)
* current selective estrogen modulator or aromatase inhibitor use
* at least 6 weeks beyond completion of definitive treatment for breast cancer
* less than 5 years from time of diagnosis.

Exclusion Criteria:

* less than 6-month life expectancy
* current steroid use
* severe depression or anxiety
* severe hepatic impairment
* concurrent use of moderate or strong CYP3A inhibitors
* current receipt of hospice care
* severe mental illness
* current use of greater than 40 morphine milligram equivalents daily
* diagnosis of obstructive sleep apnea, narcolepsy or other sleep related illness other than insomnia
* pregnancy
* treatment with alternate pharmacotherapy for insomnia at the time of trial initiation
* menstrual cycle within the past year

Participant flow

Outcome results

• Participant Reported Insomnia Symptoms Evaluated Using the Insomnia Severity Index (ISI) (Primary), Mean, ISI score: Suvorexant With Information on Sleep Hygiene 9.5 +/- 13.4; Placebo With Information on Sleep Hygiene 12.0 +/- 8.2
• Vasomotor Symptoms Assessed Using the Hot Flash Related Daily Interference Scale (Secondary), Mean, Scores on a scale: Suvorexant With Information on Sleep Hygiene 3.6 +/- 3.7; Placebo With Information on Sleep Hygiene 2.0 +/- 3.4
• Quality of Life Evaluated Using the SF-36 (Secondary), Mean, General Health Domain Score: Suvorexant With Information on Sleep Hygiene 46.6 +/- 41.6; Placebo With Information on Sleep Hygiene 51.6 +/- 12.6
• Quality of Life Evaluated Using the Cancer Problems in Living Scale (CPIL) (Secondary), Mean, Scores on a scale: Suvorexant With Information on Sleep Hygiene 14.5 +/- 2.1; Placebo With Information on Sleep Hygiene 10 +/- 7.1
• Pain Evaluation Evaluated Using the Brief Pain Inventory (BPI) (Secondary), Mean, Score on a scale: Suvorexant With Information on Sleep Hygiene 1.9 +/- 2.7; Placebo With Information on Sleep Hygiene 2.2 +/- 2.6
• Number of Participants Reported as Adherent Using the Simplified Medication Adherence Questionnaire (SMAQ) (Secondary), Count of participants, Participants: Suvorexant With Information on Sleep Hygiene 2; Placebo With Information on Sleep Hygiene 3
• Vasomotor Symptoms Assessed Using the Hot Flash Related Daily Interference Scale (Secondary), Mean, Scale Score: Suvorexant With Information on Sleep Hygiene 2.5; Placebo With Information on Sleep Hygiene 3 +/- 2.8
• Participant Reported Insomnia Symptoms Evaluated Using the Insomnia Severity Index (ISI) (Secondary), Mean, ISI score: Suvorexant With Information on Sleep Hygiene 14.5 +/- 4.6; Placebo With Information on Sleep Hygiene 12.7 +/- 5.5
• Pain Evaluation Evaluated Using the Brief Pain Inventory (BPI) (Secondary), Mean, Scores on a scale: Suvorexant With Information on Sleep Hygiene 0.6 +/- 0.9; Placebo With Information on Sleep Hygiene 5.1 +/- 2.1

Adverse events

Time frame: From enrollment until 4 weeks

Limitations and caveats: In this trial, there was low accrual with 2 participants in one group and 3 participants in the other representing 11% of the intended sample size. As a result any summary statistics are at high risk of being misleading. As a result, no conclusions or statistical evaluation can or should be completed.

• Study Protocol and Statistical Analysis Plan (PDF, 2025-07-31)

• Sarah Marrison, MD PhD, Principal investigator, Medical University of South Carolina