Modafinil to Reduce Persistent Fatigue in Patients Following Treatment for Cancer

Fatigue is a very common and troublesome side effect experienced in cancer patients before,
during and after chemotherapy and radiation treatment. This protocol will increase knowledge
about the occurrence and treatment of fatigue that develops during cancer treatments with
the rationale that:

1. better control of the fatigue reported by patients during and following cancer
treatment is needed,

2. there are few systematic data on the etiology of fatigue following cancer treatment,
and

3. there is evidence indicating that chemotherapy is associated with cognitive
dysfunction.

Comparisons: In this randomized, placebo-controlled study of cancer patients following their
chemotherapy or radiation therapy, we will assess the efficacy of modafinil for relieving
cancer-related fatigue by actigraphy and for preventing or improving cognitive dysfunction
by computer-generated tasks that have previously been utilized to examine drug-induced
changes in performance (CDR Cognitive Assessment). Additional outcome measures will include
the Fatigue Symptom Checklist, POMS, Fatigue Severity Scale, sleepiness measured by the
Epworth Sleepiness Scale, cytokine blood levels, depression measured by the CES-D, and
psychological adjustment to cancer measured by the Mini-MAC.

The primary objective is to:

- compare changes in patient reported fatigue following completion of chemotherapy and/or
radiation treatment for cancer in patients who receive open-label modafinil (PROVIGIL®)
for 4 weeks

Secondary objectives are to:

- assess the persistence of any effect found with a randomized trial of responders to
modafinil or placebo for 4 weeks (responders are those who report at least a 1 point
decrease in fatigue as measured by the Brief Fatigue Inventory)

- assess the degree to which modafinil can prevent or reduce cognitive dysfunction
following treatment for cancer

- investigate potential relationships among depression, fatigue, cytokines, and cognitive
dysfunction

Anticipated results could provide potentially important new information with regard to
clinical, theoretical, and methodologic applications; that is, improved pharmacologic and
perhaps behavioral control of the debilitating fatigue commonly experienced by patients
undergoing treatment for cancer.

Inclusion Criteria:

- Patient is longer than one-month post chemotherapy and/or radiation treatment for an
initial diagnosis of cancer

- Patient is 18 years of age or older

- Patient is able to swallow medication

- Patient has a Brief Fatigue Inventory (BFI) question #3 "fatigue worst" score of 2 or
greater

Exclusion Criteria:

- Patient has ever taken modafinil (PROVIGIL)

- Patient has taken an anticonvulsant for a seizure disorder; has taken any of the
following on a regular basis within the past 30 days, a psychostimulant (e.g.,
amphetamines, methylphenidate [Ritalin], pemoline [Cylert]), or a monoamine oxidase
inhibitor (MAOIs)

- Patient has a history of clinically significant cardiac disease, uncontrolled
hypertension, alcohol or drug abuse, severe headaches, glaucoma, seizure disorder,
narcolepsy, a psychotic disorder, or Tourette's syndrome

- Patient presently taking on a regular basis:

- an anticoagulant (Coumadin [warfarin], heparin); note that low dose Coumadin (1
mg by mouth daily) given for maintenance of venous access devices is acceptable

- alpha-interferon or interleukin-2,

- a corticosteroid (dexamethasone, prednisone, prednisolone)

- Patient has a narrowing (pathological or iatrogenic) or obstruction of the
gastrointestinal tract

- Patient is currently pregnant or nursing (if currently using a steroidal
contraceptive for fertility control, participant must agree to use a barrier method
of contraception during the study and for one full menstrual cycle following the
study

- Patient has uncontrolled anemia; receiving treatment for anemia and currently stable
is acceptable