Combination Therapy for Cancer-Related Fatigue

Overseen By Sriram Yennu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Cognitive failure, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining psychoeducational interventions, such as education and counseling, with an open-label placebo (where participants know they are receiving a placebo) can reduce fatigue in people with advanced cancer. It compares the effects of the combination, the interventions alone, and the placebo alone. Participants must have experienced significant fatigue for at least two weeks and be patients at MD Anderson Cancer Center or its Houston locations.

As a Phase 2 and Phase 3 trial, this research evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in cancer care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In a previous study, open-label placebos, where patients knew they were taking a placebo, reduced fatigue in cancer patients without significant side effects. Research has shown that psychoeducational interventions, which include education and counseling, are well-received and help manage fatigue. These approaches have a positive impact with minimal risks. Past studies indicate that both treatments are well-tolerated, suggesting they are safe options for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for cancer-related fatigue because they explore innovative approaches that diverge from typical methods. Traditional treatments often include exercise therapy, cognitive behavioral therapy, and medications like psychostimulants. However, the trial introduces a psychoeducational intervention combined with a placebo, which could harness the power of psychological and educational support to enhance the placebo effect. This approach is particularly intriguing as it could provide relief without the side effects associated with medication. Additionally, the use of an open-label placebo challenges the conventional understanding of placebo effects, potentially paving the way for new, non-pharmacological treatment strategies that are both effective and sustainable.

What evidence suggests that this trial's treatments could be effective for cancer-related fatigue?

Studies have shown that psychoeducational interventions, which include education and counseling, can significantly reduce cancer-related tiredness. Research indicates these methods positively affect both physical and emotional well-being. Previous patients reported feeling less tired when using these approaches. In this trial, some participants will receive the psychoeducational intervention alone, while others will receive it combined with an open-label placebo.

Research also suggests that open-label placebos, where patients know they are taking a placebo, can help reduce tiredness in cancer patients. Studies found that these placebos can improve quality of life and reduce tiredness symptoms within just one week. In this trial, some participants will receive the open-label placebo alone. Both treatments show promise in managing cancer-related fatigue. ^{1 2 3 4 6}

Who Is on the Research Team?

Sriram Yennu

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced, incurable metastatic cancer experiencing significant fatigue. They must be mentally clear, able to follow the study protocol, and not severely anemic. Participants should have a reasonable level of physical functioning and receive care at MD Anderson Cancer Center or its affiliates.

Inclusion Criteria

You must comprehend the study outline and sign a formalized consent.

I am willing to follow up with the research team in person or virtually.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I can complete all required forms and understand the study's recommendations.

Be pregnant or become pregnant while on study.

Have a major contraindication to placebo (e.g., allergy or hypersensitivity to study medications or their constituents), or conditions making adherence difficult as determined by the attending physician.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive psychoeducational interventions combined with an open-label placebo or psychoeducational interventions alone

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of quality of life, mood, sleep-wake activity, and cognitive measures

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Open Label Placebo
• Placebo
• Psychoeducational Intervention

Trial Overview The study tests if combining educational support and self-care strategies (psychoeducational interventions) with a known placebo can better improve life quality compared to each approach alone in managing cancer-related fatigue in patients with metastatic cancers.

How Is the Trial Designed?

Group I: Psychoeducational Intervention+Placebo Experimental Treatment 1 Intervention

Participants will be randomly assigned to 1 of 3 study groups. The study treatment participants get will be chosen by chance, like rolling the dice. Both participants and the study staff will know which treatment you were assigned:

Group II: Psychoeducational Intervention Experimental Treatment 1 Intervention

Participants will be randomly assigned to 1 of 3 study groups. The study treatment participants get will be chosen by chance, like rolling the dice. Both participants and the study staff will know which treatment you were assigned:

Group III: Open Label Placebo Experimental Treatment 1 Intervention

Participants will be randomly assigned to 1 of 3 study groups. The study treatment participants get will be chosen by chance, like rolling the dice. Both participants and the study staff will know which treatment you were assigned:

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A systematic review of 30 randomized controlled trials involving cancer-related fatigue (CRF) found a statistically significant placebo response, with a pooled standardized mean change of -0.23, indicating that patients in the placebo groups experienced a notable reduction in fatigue.

The study highlights the need for researchers to consider alternative trial designs in future CRF drug studies to better account for the placebo response, as all included trials had limitations that increased their risk of bias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression. Roji, R., Stone, P., Ricciardi, F., et al.[2022]

Cancer-related fatigue is a common and persistent issue for survivors, significantly impacting their quality of life and potentially reducing survival rates, with inflammation playing a key role in its development.

While there is no gold-standard treatment for cancer-related fatigue, various interventions such as physical activity, psychosocial support, mind-body techniques, and pharmacological options have shown beneficial effects in randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer-related fatigue--mechanisms, risk factors, and treatments. Bower, JE.[2022]

In a small study of 27 cancer patients undergoing radiation therapy, both true and sham acupuncture showed improvements in fatigue and quality of life, but the differences were not statistically significant, indicating that more research is needed to confirm these findings.

The true acupuncture group showed a greater improvement in fatigue scores compared to the sham group, suggesting potential benefits of acupuncture, but the study was underpowered, indicating that a larger trial with at least 75 subjects per group is necessary to draw more definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot, randomized, modified, double-blind, placebo-controlled trial of acupuncture for cancer-related fatigue. Balk, J., Day, R., Rosenzweig, M., et al.[2022]

In a study of 40 cancer survivors, those receiving open-label placebo (OLP) reported significant improvements in cancer-related fatigue (CRF) after 3 weeks, indicating that even when participants know they are taking a placebo, it can still be effective.

The improvement in CRF was influenced by genetic factors related to dopamine metabolism, suggesting that individual biological differences may play a role in how well placebos work for symptom management in cancer survivors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label placebo reduces fatigue in cancer survivors: a randomized trial. Zhou, ES., Hall, KT., Michaud, AL., et al.[2020]

In a study involving 84 patients with advanced cancer, an open-labeled placebo (OLP) significantly reduced cancer-related fatigue (CRF) after one week compared to a waitlist control, with a mean improvement of 6.6 points on the FACIT-F scale versus 2.1 points for the control group.

The benefits of the OLP were sustained for four weeks after the initial treatment, indicating its potential efficacy in managing fatigue in advanced cancer patients, with no significant adverse effects reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Placebo for the Treatment of Cancer-Related Fatigue in Patients with Advanced Cancer: A Randomized Controlled Trial. Yennurajalingam, S., Azhar, A., Lu, Z., et al.[2023]

Cancer-related fatigue (CRF) affects 43.0% of cancer patients, with a total prevalence of 70.7% when including mild fatigue, highlighting its significant impact on patient well-being and treatment compliance.

The study found that severe CRF prevalence varies by cancer type and treatment phase, with chemotherapy leading to a higher prevalence (33.1%) compared to surgery (22.0%) and radiotherapy (24.2%), and female patients experiencing 1.4 times more severe fatigue than males.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of cancer-related fatigue based on severity: a systematic review and meta-analysis. Kang, YE., Yoon, JH., Park, NH., et al.[2023]

Cancer-related fatigue (CRF) is a common and distressing symptom experienced by cancer patients throughout their journey, yet it is often underdiagnosed and poorly managed.

Evidence from controlled trials indicates that interventions like exercise, psycho-educational programs, and cognitive-behavioral therapy for insomnia are effective in treating CRF, highlighting the need for more rigorous studies to identify the best treatments for specific patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer-related fatigue: state of the science. Mitchell, SA.[2010]

In a study of 105 patients with cancer-related fatigue, 56% showed a significant placebo response, indicating that many patients can experience improvements in fatigue even when receiving a placebo treatment.

Worse baseline physical well-being, particularly in areas like anxiety and sleep, was linked to a higher likelihood of experiencing a placebo response, suggesting that patient characteristics should be carefully considered in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo and nocebo effects in randomized double-blind clinical trials of agents for the therapy for fatigue in patients with advanced cancer. de la Cruz, M., Hui, D., Parsons, HA., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9732231/

Open-Label Placebo for the Treatment of Cancer-Related ... Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week.

2. nature.com nature.com/articles/s41598-018-20993-y

Open-Label Placebo Treatment for Cancer-Related Fatigue Although there are some methodological limitations, a recent meta-analysis found overall moderate effect sizes for open-label placebos. While ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.12006

Open-labeled placebo for the treatment of cancer-related- ... Open labeled placebo was efficacious in reducing CRF, fatigue cluster, and QOL in fatigued advanced cancer patients at the end of one week.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02522988

The Use of an Open Label Placebo to Treat Cancer ... The purpose of this randomized-controlled, crossover pilot trial is to evaluate the feasibility, acceptability and effects of a non-deceptive (open-label) ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36106759/

Open-Label Placebo for the Treatment of Cancer ... - PubMed Open-labeled placebo was efficacious in reducing CRF and fatigue clusters in fatigued advanced cancer patients at the end of 1 week.

6. programinplacebostudies.org programinplacebostudies.org/wp-content/uploads/2018/10/Zhou2018_Article_Open-labelPlaceboReducesFatigu.pdf

Open-label placebo reduces fatigue in cancer survivors Conclusions Results demonstrate that even when administered openly, placebos improve CRF in cancer survivors and dopami- nergic systems may be associated with ...