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

212 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well methylphenidate and physical activity works in reducing cancer-related fatigue in patients who are receiving anti-PD1 immunotherapy for cancer that has spread to other places in the body. Central nervous systems stimulants, such as methylphenidate, may help to improve cognitive function. Physical activity uses techniques, such as aerobic and resistance exercises, which may help to improve quality of life. Giving methylphenidate and physical activity may help in reducing cancer-related fatigue in patients with metastatic cancer who receive anti-PD1 immunotherapy.

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.

What data supports the effectiveness of the drug methylphenidate for cancer-related fatigue?

Research shows that methylphenidate, a drug often used to treat attention issues, has been studied for its potential to help with fatigue in cancer patients. Some studies suggest it might help reduce fatigue, but results are mixed, meaning it works for some people but not for others. ^{1 2 3 4 5}

Is the combination of methylphenidate and exercise safe for treating cancer-related fatigue?

Methylphenidate has been studied for safety in treating cancer-related fatigue, showing some improvement in fatigue symptoms but also a higher rate of side effects like headache, nausea, and dry mouth compared to a placebo. In a study, 63% of patients experienced side effects, and 11% stopped treatment due to these effects. ^{2 3 5 6 7}

How does the drug methylphenidate combined with exercise help with cancer-related fatigue?

This treatment is unique because it combines methylphenidate, a drug often used to treat attention deficit hyperactivity disorder (ADHD) and fatigue, with exercise to address cancer-related fatigue. Methylphenidate works by stimulating the central nervous system to increase alertness and energy, while exercise can improve physical strength and endurance, potentially offering a more comprehensive approach to managing fatigue compared to using either method alone. ^{2 3 5 7 8}

Research Team

Sriram Yennu

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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: able to read, write and speak English

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.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

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

Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. [2013]

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

The use of methylphenidate to relieve fatigue. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

A phase II study of methylphenidate for the treatment of fatigue. [2018]

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

Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. [2022]

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

Effect of methylphenidate in patients with cancer-related fatigue: a systematic review and meta-analysis. [2022]

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

Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder. [2015]

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

Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. [2022]

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

Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study. [2017]