Methylphenidate Study in Breast or Gastrointestinal Cancer Patients

Condition(s) targeted: Breast Cancer; Fatigue; Gastrointestinal Cancer

Intervention: Methylphenidate (Drug); Placebo (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Carmen Escalante, MD, Principal Investigator, Affiliation: U.T.M.D. Anderson Cancer Center

Overall contact:
Carmen Escalante, MD, Phone: 713-745-4516

Objectives:

- To assess the efficacy of OROS Methylphenidate as compared to placebo for improvement

of fatigue in patients with breast or gastrointestinal cancer who are undergoing chemotherapy.

- To examine cytokine levels and their correlation with fatigue and cognitive function.

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

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: Drug OROS Methylphenidate HCl (Concerta) ability to control fatigue in patients with breast or gastrointestinal cancer who are going through chemotherapy treatment.

Secondary outcome: How certain cytokines change while patients undergo chemotherapy.

Detailed description: 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. A total of 50 patients will take part in this study. All will be enrolled at M. D. Anderson.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. Patient diagnosed with breast or gastrointestinal cancer undergoing chemotherapy

2. Patient is > or = 18 years of age

3. Patient has Brief Fatigue Inventory "fatigue worst" score of > or = 4 at baseline

4. Patient has an ECOG performance status of < or = 2 at baseline

5. Patient has a life expectancy > or = 6 months from the start of the study

6. 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

7. Patient must speak and understand English

8. Patient has provided written informed consent to participate in the study prior to enrollment to the study

Exclusion Criteria:

1. History of hypersensitivity reaction to methylphenidate

2. History of or current severe headaches, seizure disorder, glaucoma, major psychiatric diagnosis, narcolepsy, Tourette's syndrome, tension or agitation

3. History of clinically significant pulmonary or cardiac disease (see protocol for criteria)

4. 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) greater than 150 mm Hg or diastolic pressure consistently greater than 85 mm Hg

5. History of fibromyalgia

6. Use of alcohol while participating in the study

7. Current use of illicit drugs or history of alcohol or drug abuse and/or abuse potential (see protocol for criteria)

8. Moderate to severe depression (> or = 20 on Beck Depression Index II)

9. If taking antidepressants, no changes in dose and/or no start of new course of treatment in the last 30 days

10. Currently taking psychostimulants (including appetite suppressants), MAO inhibitors, anticoagulant therapy, or anticonvulsants

11. Current use of corticosteroids, medications, or stimulants (i. e., vivarin) used to improve fatigue symptoms

12. Use of an investigational medication within the past month

13. 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)

14. Any coexisting medical condition or are taking any concomitant medication that is likely to interfere with the safe administration of methylphenidate

15. Patients who start epoetin within 30 days prior to enrollment

16. Patients who start taking epoetin during the first week of the study

17. Hemoglobin < 9. 0 gm/dl

18. Patients with a TSH value > or = 1. 5 times the upper limit of normal (ULN)

19. Albumin value 50% lower than the lower limit of normal

20. Evidence of hepatic impairment [total bilirubin > or = 2. 5 times ULN (normal range of

0 - 1. 0 mg/dl, SGPT > or = 2. 5 times ULN)]

21. Evidence of renal impairment (serum creatinine > 2. 5 times ULN, normal range of 0. 8 -

1. 5 mg/dl)

22. A severe narrowing (pathological or iatrongenic), obstruction of the gastrointestinal tract, or gastrointestinal malabsorption

23. If taking anxiolytics, and/or hypnotics, no changes in dose and/or no start of new course of treatment in the last 30 days

24. Patients with nausea, vomiting, or diarrhea of CTCAE grade III or higher

Carmen Escalante, MD, Phone: 713-745-4516

U.T.M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Carmen Escalante, MD, Principal Investigator

The University of Texas M.D.Anderson Cancer Center

Starting date: August 2004
Last updated: May 14, 2009