Trial of a Sustained Release Methylphenidate in the Treatment of Fatigue in Cancer Patients

Study Overview
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Brief Summary
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The goal of this clinical research study is to see if the drug OROS Methylphenidate HCl (Concerta) can help to control fatigue in patients with breast, gastrointestinal, lymphoma, myeloma or lung cancer who are going through chemotherapy or hormonal treatment or have completed chemotherapy or hormonal treatment in the last 12 months. The safety of this drug will also be studied. Another goal of the study is to see how certain cytokines change while patients undergo chemotherapy or hormonal treatment.

Detailed Description
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OROS Methylphenidate HCl is a mild central nervous system stimulant. Cytokines are a type of protein found in blood. Medical researchers here at M. D. Anderson are working to see if they are related to, or can tell us something about, fatigue and its symptoms. This study will be divided into two, 14-day periods. During one of the 14-day periods, you will be given the study drug. During the other period, you will be given a placebo. A placebo is a sugar tablet that looks just like the study drug tablet. You will be randomly picked (as in the toss of a coin) to be in one of two treatment groups. In one group you will receive the study drug first and the placebo second. In the other group you receive the placebo first and the study drug second. The chance of being in either treatment group is about equal. Neither you nor the research staff will know which treatment order you are assigned to. Before treatment starts, you will fill out questionnaires about your level of fatigue, distress, symptoms, and general health. It should take about 5 minutes to complete the questionnaires. You will have a medical history, physical exam (with pulse, temperature, blood pressure), and blood work done. At the start of the study a test of the heart called an EKG will be done. At the start of the study, and after you finish the study, you will complete additional questionnaires that measure mood, fatigue, sleep, and appetite. It should take about 15 minutes to complete the questionnaires. You will also complete a series of tests for memory, visual-motor, and thinking functions. These tests should take about 30 minutes to complete. (This evaluation may take place on or before Day 1 of the study.) On Day 1, a set of study medications and a diary will be given to you. For the first fourteen days of the study, you will take the assigned study medication (either drug or placebo). Everyday you will fill out the diary, noting the time you took the study medication and answering two questions about your fatigue. On Day 7, study personnel will see you in the clinic or Ambulatory Treatment Center. The delegated research personnel will take your blood pressure and pulse and ask you about any symptoms or complaints you may have had or any medications you may have taken. On Day 14, study personnel will see you in the clinic or the Ambulatory Treatment Center where blood pressure and pulse will be measured. Unused study medication will be returned and your diary will be reviewed with the delegated research personnel. You will complete questionnaires asking about fatigue, sleep, depression, and symptoms. It should take about 15 minutes to complete them. You will also complete a series of tests for memory, visual-motor, and thinking functions. The tests should take about 30 minutes to complete. A blood draw will be done to look for changes in hemoglobin and for cytokine analysis. A new set of study medications and a diary will be given to you. You will follow the same instructions as the first time period. You will take the assigned study medication every morning and fill out the diary, noting the time you took the study medication and answering two questions about your fatigue. On Day 21, the same activities as Day 7 will occur. If you are not scheduled to come to M. D. Anderson on Day 7 and Day 21, you will take 2 separate blood pressure measurements 5 minutes apart for each day and report results within 24 hours to the research staff. If you choose to take your blood pressure measurements at home, you need to bring your monitor at study enrollment to have measurements double-checked by research staff. On Day 28, the study will end. The same activities as Day 14 will occur. In addition, you will have a physical exam. You will be asked if you prefer the first (first 2 weeks of study) or second (second 2 weeks of study) treatment phase. If you want to continue taking the OROS Methylphenidate you will be allowed to do so off-study as long as there are no medical reasons not to. This is an investigational study. The study drug has been approved for attention-deficit hyperactivity disorder but is investigational as a treatment for cancer related fatigue. The study medication and physical exams will cost you nothing. You will be reimbursed with a fixed amount of money for each scheduled study visit. The payment will be in the form of a gift card for parking expenses and a gift card for gas expenses. The study doctor or study staff can tell you more about when you will be able to receive reimbursement. A total of 50 patients will take part in this study. All will be enrolled at The University of Texas (UT) MD Anderson.

Official Title
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A Randomized, Double Blind, Two Period, Placebo-Controlled Crossover Trial of a Sustained Release Methylphenidate in the Treatment of Fatigue in Cancer Patients

Conditions
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Breast Cancer, Fatigue, Gastrointestinal Cancer

Intervention / Treatment
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* Drug: Methylphenidate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient diagnosed with breast, gastrointestinal, lymphoma, myeloma or lung cancer undergoing chemotherapy or hormonal treatment Patient is > or = 18 years of age Patient has Brief Fatigue Inventory fatigue worst score of > or = 4 at baseline Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of < or = 2 at baseline Patient has a life expectancy > or = 6 months from the start of the study Patient is using acceptable birth control methods. Female participants (if of child bearing potential and sexually active) and male participants (if sexually active with a partner of child-bearing potential) must use medically acceptable methods of birth control. Medically acceptable methods of contraception include abstinence, birth control pills, diaphragm with spermicide, condom with foam or spermicide, vaginal spermicidal suppository or surgical sterilization Patient must speak and understand English Patient has provided written informed consent to participate in the study prior to enrollment to the study Exclusion Criteria: History of hypersensitivity reaction to methylphenidate History of or current seizure disorder, glaucoma, major psychiatric diagnosis, narcolepsy, Tourette's syndrome, tension or agitation History of clinically significant cardiac disease. Uncontrolled hypertension: has not been on a stable treatment dose for the past month, or has a systolic pressure consistently (defined as 3 consecutive blood pressure readings within the last 30 days) greater than 150 mm Hg or diastolic pressure consistently greater than 85 mm Hg History of fibromyalgia Use of alcohol while participating in the study Current use of illicit drugs or history of alcohol or drug abuse and/or abuse potential (see protocol for criteria) Moderate to severe depression (> or = 20 on Beck Depression Index II) If taking antidepressants, no changes in dose and/or no start of new course of treatment in the last 30 days Currently taking psychostimulants (including appetite suppressants), monoamine oxidase (MAO) inhibitors, anticoagulant or anticonvulsant therapy Current use of corticosteroids, medications, or stimulants (i.e., vivarin) used to improve fatigue symptoms Use of an investigational medication within the past month Current use of the following herbals or supplements for fatigue relief (DHEA, SAME, ginkgo, ginseng, St. John's Wort (including DHEA, SAME, ginkgo, ginseng, St. John's Wort, metabolite, effedrin, basil, citronella, fennel, horseradish roots, lavender flowers, lemon verbena, marjoram, mint, nettle, pine needles, rosemary, sage, savory, thyme, bay, cayenne pepper, cinnamon, eucalyptus, hyssop, myrrh, oregano, peppermint, ginseng, green, black or Chinese tea, ephedra (aka - ma-huang), popotillo, and Mormon tea) Any coexisting medical condition or are taking any concomitant medication that is likely to interfere with the safe administration of methylphenidate Patients who start epoetin within 30 days prior to enrollment Patients who start taking epoetin during the first week of the study Hemoglobin < 8.0 gm/dl Patients with a thyroid-stimulating hormone (TSH) value > or = 1.5 times the upper limit of normal (ULN) Albumin value 50% lower than the lower limit of normal Evidence of hepatic impairment [total bilirubin > or = 2.5 times ULN (normal range of 0 - 1.0 mg/dl, serum glutamate pyruvate transaminase (SGPT) > or = 2.5 times ULN)] Evidence of renal impairment (serum creatinine > 2.5 times ULN, normal range of 0.8 - 1.5 mg/dl) A severe narrowing (pathological or iatrogenic), obstruction of the gastrointestinal tract, or gastrointestinal malabsorption If taking anxiolytics, and/or hypnotics, no changes in dose and/or no start of new course of treatment in the last 30 days Patients with nausea, vomiting, or diarrhea of Common Toxicity Criteria for Adverse Effects (CTCAE) grade III or higher If taking anticonvulsants for sensory neuropathy (Gabapentin or Pregabalin), no changes in dose and/or no start of new course of treatment in the last 30 days History of severe headaches within 30 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylphenidate then Placebo<br>Methylphenidate 18 mg oral daily for 2 weeks then Placebo oral daily for 2 weeks | Drug: Methylphenidate<br>* 18 mg by mouth daily for 2 weeks<br>* Other names: Methylphenidate Hydrochloride;Drug: Placebo<br>* Capsule by mouth daily for 2 weeks<br>|
| Experimental: Placebo then Methylphenidate<br>Placebo oral daily for 2 weeks then Methylphenidate 18 mg oral daily for 2 weeks | Drug: Methylphenidate<br>* 18 mg by mouth daily for 2 weeks<br>* Other names: Methylphenidate Hydrochloride;Drug: Placebo<br>* Capsule by mouth daily for 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Difference Between Post-Methylphenidate and Post-Placebo Measurement | The primary endpoint is the fatigue worst score (range: 0 - 10) on the Brief Fatigue Inventory (BFI) at the end of two-week treatment (either Methylphenidate or placebo). Worst fatigue is defined as participants' rating of worst fatigue on a scale of 0 (no fatigue) to 10 (as bad as can imagine). Since each participant is expected to receive both 2-week of Methylphenidate or 2-week placebo at different times, they serve as their own control. The outcome is the difference in fatigue worst score between post-Methylphenidate measurement and post-Placebo measurement. | At end of two 2-week treatment cycles (4 weeks total) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast Cancer, Gastrointestinal Cancer, GI Cancer, Fatigue, OROS Methylphenidate HCl, Methylphenidate, Methylphenidate Hydrochloride, Concerta, Ritalin, Placebo