Methylphenidate in Treating Patients With Fatigue Caused by Cancer

OBJECTIVES:

Primary

- Test the efficacy of long-acting methylphenidate in patients with cancer-related
fatigue as measured using an item of the Brief Fatigue Inventory.

Secondary

- Evaluate the tolerability and adverse events associated with this drug in these
patients.

- Study the effect of this drug on quality of life (QOL)-related variables (vitality,
sleep quality, overall QOL, QOL domains, other fatigue measures, and perceived
treatment efficacy) in these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to disease stage (0, I, or II vs III or IV), level of fatigue at
baseline (4-7 vs 8-10), concurrent biological therapy (yes vs no), concurrent chemotherapy
(yes vs no), and concurrent radiotherapy (yes vs no). Patients are randomized to 1 of 2
treatment arms.

- Arm I: Patients receive oral methylphenidate daily on days 1-28.

- Arm II: Patients receive oral placebo daily on days 1-28.

Patients in both arms complete questionnaires to assess their symptoms of fatigue, overall
mood, quality of life, sleep quality, and adverse effects from treatment at baseline and
once weekly for 4 weeks. Patients also complete a Symptom Experience Diary.

McNeil Consumer & Specialty Pharmaceuticals provided medication support for NCCTG N05C7.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.

Inclusion Criteria:

1. ≥ 18 years of age

2. Men or women with a history of cancer-related fatigue as defined by a score ≥ 4 on a
fatigue numerical analogue scale (0 - 10)

3. Fatigue for ≥ 1 month prior to registration

4. ECOG Performance Score (PS) 0, 1, or 2

5. Life expectancy ≥ 6 months

6. Histologic or cytologic proven cancer other than brain cancer or CNS lymphoma

7. Laboratory values obtained ≤ 30 days prior to registration:

- Hgb ≥ 10 g/dL

8. Willing and able to provide informed consent

9. Negative pregnancy test (urine or serum) done ≤ 7 days prior to registration, for
women of childbearing potential only

10. Ability to complete questionnaire(s) by themselves or with assistance

11. Biological therapy (i.e. immunotherapy, biotherapy), chemotherapy or radiation
therapy will be allowed

12. Use of a stable dose of anti-depressants (except tricyclic anti-depressants) will be
allowed

13. Erythropoietic agents to treat anemia, and steroids as a part of cancer treatment and
for symptom management (except for fatigue) will be allowed

Exclusion Criteria:

1. Hypersensitivity to methylphenidate

2. Any prior use of methylphenidate

3. Concomitant (≤ 2 weeks) use of prescription stimulants (pemoline, modafinil,
amphetamines); other medications, herbal products or dietary supplements for fatigue

4. Uncontrolled hypertension [defined as systolic blood pressure (BP) ≥ 160 mmHg and/or
diastolic BP ≥ 100 mmHg on 2 separate visits ≤ 2 months prior to randomization]; or a
resting heart rate > 100

5. Moderate or severe pain as defined by an average daily score ≥ 4 on a pain analog
scale (0 - 10)

6. Known brain metastasis or primary CNS malignancy

7. Clinically significant acute or chronic progressive or unstable neurologic (dementia,
delirium, or seizure disorder), hepatic, renal, cardiovascular, thyroid, or
respiratory disease that would limit participation in the study per MD discretion or
judgment

8. Psychiatric disorder such as manic depression, anxiety disorder, bipolar disorder,
obsessive compulsive disorder, or schizophrenia

9. Major surgery < 4 weeks prior to registration. (Note: Insertion of central venous
catheter is not considered major surgery.)

10. Using a drug contraindicated when taken concurrently with methylphenidate: coumarin
anticoagulants, anticonvulsants, tricyclic antidepressants, antipsychotics, monoamine
oxidase inhibitors, clonidine, theophylline, and pseudoephedrine

Note: use of Compazine prescribed as an antiemetic is permitted for use while
participating in this study.

11. Additional medical conditions where use of methylphenidate is contraindicated:

glaucoma, motor tics, family history or diagnosis of Tourette's syndrome, history of
drug or alcohol abuse or intestinal obstruction.

12. Pregnant women or nursing women. Women of childbearing potential who are unwilling to
employ adequate contraception. This study involves an investigational agent whose
genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are
unknown.

13. Untreated hypothyroidism (TSH ≥ 5)