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Methylphenidate and Physical Activity to Reduce Cancer Related Fatigue Due to Anti PD1 Immunotherapy

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ClinicalTrials.gov Identifier: NCT03525873
Recruitment Status : Recruiting
First Posted : May 16, 2018
Last Update Posted : July 23, 2020
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Advanced Malignant Neoplasm Metastatic Malignant Neoplasm Recurrent Malignant Neoplasm Other: Laboratory Biomarker Analysis Drug: Methylphenidate Other: Physical Activity Other: Placebo Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. 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:

I. 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:

I. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 398 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Study of Cancer Related Fatigue in Patients With Metastatic Cancer Receiving Anti-PD1 Immunotherapy
Actual Study Start Date : August 2, 2018
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ARM I (methylphenidate, physical activity)
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.
Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Methylphenidate
Given PO
Other Name: Daytrana

Other: Physical Activity
Participate in physical activity

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Placebo Comparator: ARM II (placebo, physical activity)
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.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Physical Activity
Participate in physical activity

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Assessment of MP effects on physical activity [ Time Frame: Up to 12 weeks ]
    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.

  2. Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires [ Time Frame: Up to 5 minutes during visit ]
    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

  3. Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires [ Time Frame: Up to 5 minutes during visit ]
    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

  4. Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires [ Time Frame: Up to 5 minutes during visit ]
    To be assessed using statistical methods described in primary outcomes and using outcome variables including Hospital Anxiety and Depression Scale (HADS) for anxiety/depression

  5. Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires [ Time Frame: Up to 5 minutes during visit ]
    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.

  6. Assessment of MP effects on anxiety, depressed mood, and cancer symptoms by questionnaires [ Time Frame: Up to 5 minutes during visit ]
    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).


Other Outcome Measures:
  1. Assessment of MP effects on levels of serum IL-1b, IL-1 RA, IL-6, TNF-a, IL-8,IL-10, and MCP1 [ Time Frame: At weeks 2, 6, and 10 ]
    To be assessed using blood samples obtained from participants. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Part 1: have a diagnosis of advanced cancer (defined as metastatic or recurrent) and previously received anti-PD1 immunotherapy provided that they received therapy at least 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
  • Part 1: 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: Patient 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

Exclusion Criteria:

  • 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
  • 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)
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525873


Contacts
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Contact: Sriram Yennu, MD 713-745-1613 syennu@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Sriram Yennu    713-745-2668      
Principal Investigator: Sriram Yennu         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Sriram Yennu M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03525873    
Other Study ID Numbers: 2017-0913
NCI-2018-00698 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0913 ( Other Identifier: M D Anderson Cancer Center )
First Posted: May 16, 2018    Key Record Dates
Last Update Posted: July 23, 2020
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Recurrence
Disease Attributes
Pathologic Processes
Methylphenidate
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents