Methylphenidate + Exercise for Cancer-Related Fatigue

Overseen By Sriram Yennu, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: M.D. Anderson Cancer Center

Must not be taking: MAO inhibitors, Tricyclics, Clonidine, Anticonvulsants

Disqualifiers: Cognitive failure, Glaucoma, Severe cardiac disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 4

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining methylphenidate with regular exercise can reduce fatigue in cancer patients undergoing anti-PD1 immunotherapy. Methylphenidate, a stimulant, might enhance cognitive function, while exercise could improve overall quality of life. Participants will receive either methylphenidate or a placebo, along with an exercise routine that includes walking and resistance exercises. This trial suits individuals with metastatic or recurrent cancer who experience fatigue and have previously received anti-PD1 immunotherapy. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you are not currently taking methylphenidate or have taken it within the last 10 days. Additionally, you cannot be on certain medications like monoamine oxidase inhibitors, tricyclic antidepressants, clonidine, anticoagulants, anticonvulsants, or phenylbutazone.

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

Studies have shown that methylphenidate is generally safe and well-tolerated in people with cancer-related tiredness. Some individuals may experience mild side effects, but these are not serious. Research indicates that methylphenidate does not consistently outperform a placebo (a pill with no active ingredients) in reducing tiredness.

Regarding physical activity, research shows it is safe and can help reduce tiredness in cancer patients. Exercise can also improve quality of life and lessen some side effects of cancer treatment. Studies support the benefits of exercise for those dealing with tiredness from cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for cancer-related fatigue because it combines methylphenidate, a medication known for its ability to boost alertness, with a structured physical activity regimen. Unlike many traditional treatments that focus solely on medication, this approach leverages the synergy between a stimulant and exercise, potentially offering a more comprehensive solution to fatigue. Methylphenidate acts by increasing dopamine and norepinephrine levels in the brain, enhancing focus and energy, while exercise is known to improve overall physical and mental well-being. Together, they might provide faster and more holistic relief from fatigue compared to standard treatments like rest and nutritional support.

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

Research has shown that physical activity, which participants in this trial will undertake, can help reduce cancer-related tiredness. Studies indicate that exercises like walking or lifting weights can improve both quality of life and tiredness levels in cancer patients. In this trial, some participants will receive the medication methylphenidate alongside physical activity. For methylphenidate, results are less clear. Some studies found it no better than a placebo for reducing tiredness in cancer patients. However, another study showed some improvement in tiredness with higher doses over longer periods. Overall, exercise is strongly supported for alleviating cancer-related tiredness, while methylphenidate shows mixed results. ^{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 with metastatic or recurrent cancer who have fatigue from recent anti-PD1 immunotherapy. They must be able to communicate in English, consent to the study, and participate in follow-up calls. Excluded are those with glaucoma, certain medication use (anticoagulants, anticonvulsants), cognitive failure, specific heart diseases, or severe allergies to trial medications.

Inclusion Criteria

Part 1: be able to understand the description of the study and give written informed consent

I have a phone to be contacted by the research team.

Part 2: have a hemoglobin level of >=8 g/dL within 2 weeks of enrollment

Exclusion Criteria

Part 2: patients with Cut Down, Annoyed, Guilty and Eye Opener-Adapted to Include Drugs (CAGE-AID) >= 2

I do not have severe heart disease.

Part 2: have a major contraindication to MP (e.g., allergy/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 methylphenidate or placebo and engage in physical activity to reduce cancer-related fatigue

2 weeks

4 visits (in-person)

Extended Treatment

Participants may continue methylphenidate at the discretion of the treating physician for up to 12 weeks

Up to 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Methylphenidate
• Physical Activity

Trial Overview The study tests if methylphenidate combined with physical activity reduces fatigue in patients undergoing anti-PD1 immunotherapy for advanced cancer. It compares the effects of a stimulant drug and exercise routines against usual care without these interventions.

How Is the Trial Designed?

Group I: ARM I (methylphenidate, physical activity) Experimental Treatment 5 Interventions

Patients receive methylphenidate PO BID for up to 2 weeks in the absence of disease progression or unacceptable toxicity. Patients also complete physical activity consisting of walking and resistance exercise over 25-40 minutes QD 4 days a week. After 2 weeks, patients may continue methylphenidate at the discretion of the treating physician for up to 12 weeks in the absence of disease progression or unacceptable toxicity.

Group II: ARM II (placebo, physical activity) Placebo Group 5 Interventions

Patients receive a matched placebo PO BID and complete physical activity as in Arm I. Treatment continues for up to 2 weeks in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Dexmethylphenidate extended release (d-MPH-ER) significantly improved ADHD symptoms in children and adolescents compared to placebo, with 67.3% of patients showing substantial improvement on the Clinical Global Impressions scale.

While d-MPH-ER was effective, it was associated with a higher rate of reported adverse events (49.1% vs. 25.5% for placebo), indicating the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder. Greenhill, LL., Muniz, R., Ball, RR., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11520668/

Putting methylphenidate for cancer-related fatigue to rest? Methylphenidate, while safe and well-tolerated, was no more effective than placebo at relieving fatigue after 6 (±2) weeks.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02639

Methylphenidate Versus Placebo for Treating Fatigue in ... After 6 ± 2 weeks of treatment, methylphenidate was not superior to placebo for treating fatigue in advanced cancer. Methylphenidate was safe and well- ...

3. medicaljournalssweden.se medicaljournalssweden.se/actaoncologica/article/view/24156/45383

Methylphenidate for treating fatigue in palliative cancer care The treatment was assessed as being effective in 51 patients (46%). Twenty-six patients (23%) experienced AEs that were generally mild, ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0885392425002052

Methylphenidate-type Psychostimulants for Cancer ... In sensitivity analysis following 8 weeks or more of methylphenidate-equivalent doses ≥10 mg/d, significant FACIT-F improvement was observed in the MPD group ( ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00376675

Methylphenidate in Treating Patients With Fatigue Caused ... It is not yet known whether methylphenidate is more effective than a placebo in relieving fatigue and improving quality of life in patients with cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2917307/

Phase III, Randomized, Double-Blind, Placebo-Controlled ... Pharmacologic interventions with methylphenidate have suggested improvements in cancer-related fatigue, depressive symptoms, somnolence, and cognitive ...