Advanced Malignant NeoplasmPhase 3NCT03525873
A Study of Cancer Related Fatigue in Patients With Metastatic Cancer Receiving Anti-PD1 Immunotherapy
A Phase 3 study testing Laboratory Biomarker Analysis, Methylphenidate and Physical Activity in people with Advanced Malignant Neoplasm and Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm
- What is being tested?
- Laboratory Biomarker Analysis, Methylphenidate and Physical Activity
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 212 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2018to 31 Dec 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Part 1: have a diagnosis of metastatic or recurrent cancer and previously received anti PD1 immunotherapy provided that they received therapy up to 1 month prior to enrollment
- Part 1: be willing to engage in follow-up telephone calls with a research staff
- Part 1: have telephone access so they can be contacted by the research staff
- Part 1: hemoglobin level of >= 8 g/dL within 2 weeks of enrollment
- Packed red blood cell (PRBC) transfusions will be allowed to patients with hemoglobin < 8 g/dl
- Part 1: be able to understand the description of the study and give written informed consent
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- Part 1: able to read, write and speak English
- Part 2: have a diagnosis of metastatic or recurrent cancer and previously received anti PD1 immunotherapy provided that they received therapy up to 1 month prior to enrollment
- Part 2: be willing to engage in follow-up telephone calls with a research staff
- Part 2: have telephone access so they can be contacted by the research staff
- Part 2: have a hemoglobin level of >=8 g/dL within 2 weeks of enrollment
- PRBC transfusions will be allowed to patients with hemoglobin < 8 g/dl
- Part 2: be able to understand the description of the study and give written or verbal informed consent
- Part 2: able to read, write and speak English
- Part 2: presence of fatigue as defined FACIT-F subscale of =< 34 on a 0 to 52 scale (in which 52 = no fatigue and 0 = worst possible fatigue)
- Part 2: not currently taking methylphenidate, or have taken it within the previous 10 days
- Part 2: able to complete the baseline assessment forms
- Part 2: able to understand the recommendations for participation in the study
- Part 2: can be enrolled directly to part 2 independent of part 1 if on immunotherapy and having a FACIT-F fatigue =< 34, and able to complete baseline assessment and bloodwork as detailed in Part 1 at baseline and day 14 +/-3 days. Treating Oncologist should agree for participation in the intervention trial
Who cannot join
- Part 1: patients will be excluded if (1) have clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of >= 13 at baseline completed in person, by phone, or via video-conference
- Part 2: Patients will be excluded if (1) have clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of >= 13 at baseline completed in person, by phone, or via video-conference
- 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
- Part 2: on monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine
- Part 2: history of glaucoma
- Part 2: history of have severe cardiac disease (New York Heart Association functional class III or IV)
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- Part 2: tachycardia and/or uncontrolled hypertension
- Part 2: currently receiving anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and/or tricyclic drugs (imipramine, clomipramine, or desipramine)
- Part 2: patients with Cut Down, Annoyed, Guilty and Eye Opener-Adapted to Include Drugs (CAGE-AID) >= 2
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the effects of methylphenidate plus physical activity (MP) compared to placebo plus physical activity (PL) in reducing cancer-related fatigue (CRF) in patients with metastatic cancer on anti-PD1 immunotherapy, as measured by changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale scores after 2 weeks of intervention.
SECONDARY OBJECTIVES:
- To explore the effect of MP on anxiety (Hospital Anxiety and Depression Scale [HADS]), depressed mood (HADS), cancer symptoms (Edmonton Symptom Assessment Scale (ESAS), physical activity (mean day time activity as measured by actigraphy), and serum levels of inflammatory cytokines (IL-1beta, IL-1 RA, IL-6, TNF-alpha, IL-8, IL-10, and MCP1), before and after treatment.
EXPLORATORY OBJECTIVES:
- To determine the frequency and factors associated with CRF as assessed by FACIT-F, Patient-Reported Outcomes Measurement Information System Fatigue (PROMIS-F), Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), actigraphy, Edmonton Symptom Assessment System (ESAS), and serum levels of inflammatory cytokines (IL-1beta, IL-1 RA, IL-6, TNF-alpha, IL-10, IL-8, MCP-1), before and during 4 initial doses of Immunotherapy.
II. To explore the effects of MP on percentage (%) of patients with dose reduction and/or discontinuation anti-PD1 immunotherapy due to CRF.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive methylphenidate orally (PO) twice daily (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 once daily (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.
ARM II: Patients receive a matched placebo PO BID and complete physical activity as in Arm I.
- Being tested
- Laboratory Biomarker Analysis, Methylphenidate, Physical Activity, Placebo, Quality-of-Life Assessment
- Medical subject headings
- Neoplasm Metastasis, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Correlative studies
MethylphenidateDrug
Also called Daytrana
Given PO
Physical ActivityOther
Participate in physical activity
PlaceboOther
Also called placebo therapy, PLCB, sham therapy
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| ARM I (methylphenidate, physical activity) | Experimental | 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. Receives: Other: Laboratory Biomarker Analysis; Drug: Methylphenidate; Other: Physical Activity; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| ARM II (placebo, physical activity) | Placebo comparator | 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. Receives: Other: Laboratory Biomarker Analysis; Other: Physical Activity; Other: Placebo; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the effects of methylphenidate (MP) plus physical activity in reducing cancer-related fatigue (CRF)
Effects of MP to be compared to placebo plus physical activity results. To be as measured by changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) sub-scale scores. A t test will be used to evaluate the difference between groups unless the data appear to be non-normally distributed, in which case a Wilcoxon rank-sum test will be used to evaluate the difference between groups.
Measured: Up to 12 weeks
Secondary outcomes (6)
Assessment of MP effects on physical activity
To be measured by mean day time activity (actigraphy). To be evaluated using descriptive statistical analyses. A t test will be used to evaluate the difference between groups unless the data appear to be non-normally distributed, in which case a Wilcoxon rank-sum test will be used to evaluate the difference between groups. Will summarize percentage (%) of patients with stable CRF scores, % patients who had dose change and/ or discontinuation of anti-PD1 immunotherapy due to CRF.
Measured: Up to 12 weeks
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
To be assessed using statistical methods described in primary outcomes and using outcome variables including Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) for fatigue dimensions
Measured: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
To be assessed using statistical methods described in primary outcomes and using outcome variables including Patient-Reported Outcomes Measurement Information System Fatigue (PROMIS) for fatigue dimensions
Measured: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
To be assessed using statistical methods described in primary outcomes and using outcome variables including Hospital Anxiety and Depression Scale (HADS) for anxiety/depression
Measured: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
To be assessed using statistical methods described in primary outcomes and using outcome variables including Functional Assessment of Cancer Therapy-General (FACT-G) for Quality of Life.
Measured: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
To be assessed using statistical methods described in primary outcomes and using outcome variables including Edmonton Symptom Assessment System (ESAS), (0-10 scale for sleep disturbance, fatigue, and drowsiness).
Measured: Up to 5 minutes during visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start2 Aug 2018
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 212 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sriram Yennu, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03525873
- Sponsor's protocol ID
- 2017-0913
- Other IDs
- NCI-2018-00698, 2017-0913
- Status last verified
- Oct 2026
- First submitted
- 2 May 2018
- Last updated
- 6 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Cancer Related Fatigue in Patients With Metastatic Cancer Receiving Anti-PD1 Immunotherapy
- ClinicalTrials.gov ID
- NCT03525873
- Acronym / sponsor ID
- 2017-0913
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 212 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 2 Aug 2018 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 16 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- To determine the effects of methylphenidate plus physical activity (MP) compared to placebo plus physical activity (PL) in reducing cancer-related fatigue (CRF) in patients with metastatic cancer on anti-PD1 immunotherapy, as measured by changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale scores after 2 weeks of intervention.
SECONDARY OBJECTIVES:
- To explore the effect of MP on anxiety (Hospital Anxiety and Depression Scale [HADS]), depressed mood (HADS), cancer symptoms (Edmonton Symptom Assessment Scale (ESAS), physical activity (mean day time activity as measured by actigraphy), and serum levels of inflammatory cytokines (IL-1beta, IL-1 RA, IL-6, TNF-alpha, IL-8, IL-10, and MCP1), before and after treatment.
EXPLORATORY OBJECTIVES:
- To determine the frequency and factors associated with CRF as assessed by FACIT-F, Patient-Reported Outcomes Measurement Information System Fatigue (PROMIS-F), Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF), actigraphy, Edmonton Symptom Assessment System (ESAS), and serum levels of inflammatory cytokines (IL-1beta, IL-1 RA, IL-6, TNF-alpha, IL-10, IL-8, MCP-1), before and during 4 initial doses of Immunotherapy.
II. To explore the effects of MP on percentage (%) of patients with dose reduction and/or discontinuation anti-PD1 immunotherapy due to CRF.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive methylphenidate orally (PO) twice daily (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 once daily (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.
ARM II: Patients receive a matched placebo PO BID and complete physical activity as in Arm I.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARM I (methylphenidate, physical activity) | Experimental | Other: Laboratory Biomarker Analysis, Drug: Methylphenidate, Other: Physical Activity, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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. |
| ARM II (placebo, physical activity) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Physical Activity, Other: Placebo, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients 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 may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Part 1: have a diagnosis of metastatic or recurrent cancer and previously received anti PD1 immunotherapy provided that they received therapy up to 1 month prior to enrollment
- Part 1: be willing to engage in follow-up telephone calls with a research staff
- Part 1: have telephone access so they can be contacted by the research staff
- Part 1: hemoglobin level of >= 8 g/dL within 2 weeks of enrollment
- Part 1: be able to understand the description of the study and give written informed consent
Key exclusion criteria (9 listed)
- Part 1: patients will be excluded if (1) have clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of >= 13 at baseline completed in person, by phone, or via video-conference
- Part 2: Patients will be excluded if (1) have clinical evidence of cognitive failure as evidenced by Memorial Delirium Assessment Scale score of >= 13 at baseline completed in person, by phone, or via video-conference
- 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
- Part 2: on monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine
- Part 2: history of glaucoma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisCorrelative studies | Other | ARM I (methylphenidate, physical activity), ARM II (placebo, physical activity) |
| MethylphenidateAlso: DaytranaGiven PO | Drug | ARM I (methylphenidate, physical activity) |
| Physical ActivityParticipate in physical activity | Other | ARM I (methylphenidate, physical activity), ARM II (placebo, physical activity) |
| PlaceboAlso: placebo therapy, PLCB, sham therapyGiven PO | Other | ARM II (placebo, physical activity) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | ARM I (methylphenidate, physical activity), ARM II (placebo, physical activity) |
| Questionnaire AdministrationAncillary studies | Other | ARM I (methylphenidate, physical activity), ARM II (placebo, physical activity) |
Primary outcome
Assessment of the effects of methylphenidate (MP) plus physical activity in reducing cancer-related fatigue (CRF)
Time frame: Up to 12 weeks
Effects of MP to be compared to placebo plus physical activity results. To be as measured by changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) sub-scale scores. A t test will be used to evaluate the difference between groups unless the data appear to be non-normally distributed, in which case a Wilcoxon rank-sum test will be used to evaluate the difference between groups.
6 secondary outcomes
Assessment of MP effects on physical activity
Time frame: Up to 12 weeks
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
Time frame: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
Time frame: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
Time frame: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
Time frame: Up to 5 minutes during visit
Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires
Time frame: Up to 5 minutes during visit
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sriram Yennu principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Laboratory Biomarker Analysis, Methylphenidate and Physical Activity in people with Advanced Malignant Neoplasm and Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the effects of methylphenidate (MP) plus physical activity in reducing cancer-related fatigue (CRF) (time frame: Up to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.