Combination Therapy for Sleep Disturbance in Cancer

Overseen By Sriram Yennu

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Steroids, Antidepressants, Stimulants, others

Disqualifiers: Psychiatric illness, Sleep disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

188 Participants Needed

Trial Summary

What is the purpose of this trial?

To learn if Cognitive Behavior Therapy (called CBT), combined with either Bright Light Therapy (called BLT), methylphenidate, and/or melatonin, can help improve sleep and other related symptoms such as fatigue, anxiety, and depression in cancer patients. This is an investigational study. In this study, BLT, Methylphenidate and Melatonin will be compared to their placebos.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you must be on stable doses of any hypnosedative drugs, stimulants, or antidepressants for at least 1 month before joining. You cannot use certain medications like systemic anti-inflammatory drugs, monoamine oxidase inhibitors, tricyclic antidepressants, or anticoagulants.

What data supports the effectiveness of this treatment for sleep disturbance in cancer patients?

Research shows that cognitive behavioral therapy for insomnia (CBT-I) is effective in improving sleep quality and reducing insomnia in cancer patients, with benefits that last even after the treatment ends. This suggests that CBT-I, as part of a combination therapy, could be beneficial for sleep disturbances in cancer patients. ^{1 2 3 4 5}

Is cognitive behavioral therapy for insomnia (CBT-I) safe for cancer patients?

Cognitive behavioral therapy for insomnia (CBT-I) is generally considered safe for cancer patients and has been shown to improve sleep, mood, fatigue, and overall quality of life without significant safety concerns. ^{2 3 4 6 7}

How is Cognitive Behavior Therapy (CBT) unique for treating sleep disturbances in cancer patients?

Cognitive Behavior Therapy (CBT) is unique for treating sleep disturbances in cancer patients because it focuses on changing negative thought patterns and behaviors that contribute to sleep problems, rather than relying on medication. This approach can be particularly beneficial for cancer patients who may already be taking multiple medications and prefer a non-drug treatment option. ^{8 9 10 11 12}

Research Team

Sriram Yennu, MD

Principal Investigator

MD Anderson

Eligibility Criteria

This trial is for English-speaking cancer patients with sleep issues, stable or no pain, and a life expectancy of over a year. They must be cognitively able to participate and not have severe psychiatric illnesses, certain sleep disorders, or be on specific medications that could interfere with the study.

Inclusion Criteria

I have been sleeping poorly for at least 2 weeks.

Ability to communicate in English

My pain is either nonexistent, mild, or stable on my current pain medication.

Exclusion Criteria

I am not taking MOI, tricyclic antidepressants, or anticoagulants.

I have high anxiety or depression, or I've been on a stable dose of antidepressants for at least 1 month.

I have been on a stable dose of sleep or stimulant medication for at least 1 month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cognitive Behavior Therapy (CBT) combined with Bright Light Therapy (BLT), Methylphenidate, and/or Melatonin for 6 weeks

6 weeks

Weekly visits for CBT, daily BLT sessions

Follow-up

Participants are monitored for sleep quality and other symptoms at 3- and 6-months post-intervention

6 months

Treatment Details

Interventions

• Bright Light Therapy
• Cognitive Behavior Therapy
• Melatonin
• Methylphenidate

Trial Overview The study tests if Cognitive Behavior Therapy (CBT) combined with Bright Light Therapy (BLT), methylphenidate, melatonin, or their placebos can improve sleep quality and reduce fatigue, anxiety, and depression in advanced cancer patients.

Participant Groups

Group I: Placebo (CLT+ placebo MT + placebo MP with CBT) Experimental Treatment 2 Interventions

Patients receive placebo Melatonin (called placebo MT) PO QD for 6 weeks, placebo Methylphenidate (called placebo MP) PO BID for 6 weeks, Control Light Therapy (called CLT) for 30 minutes daily for 6 weeks and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks.

Group II: Methylphenidate (CLT + placebo MT + MP with CBT) Experimental Treatment 1 Intervention

Patients receive Control Light Therapy (called CLT) for 30 minutes daily for 6 weeks, placebo Melatonin (called placebo MT) PO QD for 6 weeks, Methylphenidate (called MP) PO BID for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks.

Group III: Combination Therapy (BLT+MT+MP with CBT) Experimental Treatment 3 Interventions

Patients receive Melatonin (called MT) PO QD for 6 weeks, Methylphenidate (called MP) PO BID for 6 weeks, Bright Light Therapy (called BLT) for 30 minutes daily for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks.

Group IV: Bright light and Melatonin (BLT + MT+ placebo MP with CBT) Experimental Treatment 2 Interventions

Patients receive Bright Light Therapy (called BLT) for 30 minutes daily for 6 weeks, Melatonin (called MT) PO QD for 6 weeks, placebo Methylphenidate (called placebo MP) PO BID for 6 weeks, and Cognitive Behavior Therapy (called CBT) weekly for 6 weeks.

Cognitive Behavior Therapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cognitive Behavioral Therapy for:

• Chronic pain management
• Anxiety disorders
• Depressive disorders

Approved in European Union as Cognitive Behavioural Therapy for:

• Chronic pain management
• Anxiety disorders
• Depressive disorders
• Post-traumatic stress disorder

Approved in Canada as Cognitive Behavioral Therapy for:

• Chronic pain management
• Anxiety disorders
• Depressive disorders

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

In a study of 57 women with chronic insomnia related to breast cancer, cognitive behavioral therapy (CBT) led to significant subjective sleep improvements, which were best predicted by reduced dysfunctional beliefs about sleep and higher treatment expectancies.

At the 6-month follow-up, adherence to behavioral strategies was crucial for maintaining subjective sleep improvements, although these factors did not significantly correlate with objective sleep measures from polysomnography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictors of the effect of cognitive behavioral therapy for chronic insomnia comorbid with breast cancer. Tremblay, V., Savard, J., Ivers, H.[2018]

Cognitive Behavioral Therapy for Insomnia (CBT-I) has been shown to significantly improve sleep quality and psychological outcomes in cancer patients and survivors, based on a review of 12 studies.

CBT-I not only enhances sleep but may also positively affect mood, fatigue, and overall quality of life, and it can be delivered through various methods to reach more patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. Garland, SN., Johnson, JA., Savard, J., et al.[2022]

Cognitive behavioral therapy (CBT) techniques, such as stimulus control and relaxation, can effectively address sleep issues in cancer patients, who often face unique challenges that worsen their sleep problems.

The article emphasizes the importance of tailoring CBT techniques to individual factors like age, gender, and cancer history to enhance their effectiveness in improving sleep quality for cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Sleep in Cancer Patients: Research, Techniques, and Individual Considerations. Melton, L.[2020]

Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective in reducing insomnia and improving sleep quality in breast cancer survivors, with a significant pooled effect size of -0.779 based on 14 randomized controlled trials involving 1363 participants.

The benefits of CBT-I for insomnia persist over time, showing medium-to-large effect sizes at both short-term (within six months) and long-term (12 months) follow-ups, indicating its lasting impact on sleep quality for women treated for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of cognitive behavioral therapy for insomnia in breast cancer: A meta-analysis. Ma, Y., Hall, DL., Ngo, LH., et al.[2022]

Cognitive Behavioral Therapy for Insomnia (CBT-I) significantly reduces insomnia severity, sleep onset latency, and wake after sleep onset in cancer patients, while improving sleep efficiency, based on a meta-analysis of 16 trials with 1523 participants.

Group CBT-I is the most effective delivery format, showing sustained improvements in sleep efficiency and total sleep time at short-term follow-up, although the benefits diminish over time, highlighting the need for further high-quality studies to confirm long-term efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy for insomnia in cancer patients: a systematic review and network meta-analysis. Gao, Y., Liu, M., Yao, L., et al.[2022]

A study involving 101 women undergoing chemotherapy for breast cancer found that combined cognitive behavioral therapy for insomnia and bright light therapy (CBT-I + Light) significantly improved insomnia symptoms compared to standard treatment with relaxation audio (TAU+), with a moderate effect size (ES = 0.69).

CBT-I + Light also led to greater improvements in sleep efficiency, fatigue, and daytime sleep-related impairment immediately after the intervention, suggesting it is an effective approach to manage sleep issues and fatigue during chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Light enhanced cognitive behavioral therapy for insomnia and fatigue during chemotherapy for breast cancer: a randomized controlled trial. Bean, HR., Diggens, J., Ftanou, M., et al.[2022]

Cognitive behavior therapy for insomnia (CBT-I) significantly improved sleep efficiency by 15.5% in cancer survivors, based on a review of 8 studies involving 752 participants, demonstrating its efficacy in treating insomnia in this population.

Patients receiving CBT-I experienced substantial reductions in sleep latency and wake after sleep onset, with durable effects lasting up to 6 months, supporting a strong recommendation for its use among cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors. Johnson, JA., Rash, JA., Campbell, TS., et al.[2022]

Integrated cancer therapy focuses on a disease-oriented approach to treatment, rather than relying solely on specific specialties or modalities, which can lead to more tailored and effective care for patients.

The therapy involves two key phases: first, identifying the reasons for treatment failures in various cancer presentations, and second, combining different treatment methods to enhance overall effectiveness by compensating for the weaknesses of individual therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symposium theme: a conceptual approach to integrated cancer therapy. Johnson, RE.[2019]

Immune-checkpoint inhibitors (ICIs), especially those targeting the PD-1/PD-L1 pathway, have significantly changed cancer treatment over the past decade, but many patients still experience resistance and do not achieve a cure with ICI monotherapy.

Combining ICIs with other therapies, such as chemotherapy, radiotherapy, or targeted therapies, shows promise in overcoming resistance and enhancing the immune response against cancer, as supported by various preclinical and clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associating Immunotherapy and Targeted Therapies: Facts and Hopes. Ladoire, S., Rébé, C., Ghiringhelli, F.[2023]

Cancer immunotherapy, including immune checkpoint blockade and CAR T-cell therapy, has shown significant success in treating melanoma and other cancers, but many patients still experience immune evasion and do not respond to these treatments.

Combining immune checkpoint inhibitors with other therapies, such as chemotherapy and radiotherapy, may enhance treatment effectiveness by increasing tumor immunogenicity, reversing tumor immunosuppression, and reducing tumor burden, thus improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinatorial Approach to Improve Cancer Immunotherapy: Rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System. Joshi, S., Durden, DL.[2020]

Recent clinical trials have established immunotherapy, including immune checkpoint blockade and CAR T-cell therapy, as a significant treatment option for cancer, alongside traditional methods like surgery and chemotherapy.

To enhance the effectiveness of immunotherapy, combining different agents that target immune resistance mechanisms is crucial, as current therapies only provide durable benefits to a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer immunotherapy: Strategies for personalization and combinatorial approaches. Sathyanarayanan, V., Neelapu, SS.[2022]

Recent studies have shown that immune checkpoint inhibitors can effectively enhance the immune response against cancers like metastatic melanoma, kidney cancer, and non-small cell lung cancer, particularly when used after initial chemotherapy.

Despite their promise, these treatments only benefit about 20%-25% of unselected patients, highlighting the need for reliable biomarkers, such as PD-L1, to predict which patients are most likely to respond to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Immunotherapy and Lung Cancer. Sánchez de Cos Escuín, J.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Predictors of the effect of cognitive behavioral therapy for chronic insomnia comorbid with breast cancer. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Sleeping well with cancer: a systematic review of cognitive behavioral therapy for insomnia in cancer patients. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Cognitive Behavioral Therapy for Sleep in Cancer Patients: Research, Techniques, and Individual Considerations. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of cognitive behavioral therapy for insomnia in breast cancer: A meta-analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Cognitive behavior therapy for insomnia in cancer patients: a systematic review and network meta-analysis. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Light enhanced cognitive behavioral therapy for insomnia and fatigue during chemotherapy for breast cancer: a randomized controlled trial. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of randomized controlled trials of cognitive behavior therapy for insomnia (CBT-I) in cancer survivors. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Symposium theme: a conceptual approach to integrated cancer therapy. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Associating Immunotherapy and Targeted Therapies: Facts and Hopes. [2023]

10. Egypt pubmed.ncbi.nlm.nih.gov

Combinatorial Approach to Improve Cancer Immunotherapy: Rational Drug Design Strategy to Simultaneously Hit Multiple Targets to Kill Tumor Cells and to Activate the Immune System. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Cancer immunotherapy: Strategies for personalization and combinatorial approaches. [2022]

12. Spain pubmed.ncbi.nlm.nih.gov

New Immunotherapy and Lung Cancer. [2018]