Multimodal Therapy for the Treatment of Sleep Disturbance in Patients With Advanced Cancer

Counseling and Physical Activity:

If you are found eligible and agree to take part, you will meet with a counselor. You will be
asked to discuss your thoughts and feelings on different topics related to your well-being.
The counseling session will last about 30 minutes and will be audiotaped for quality control.

You will be given a watch to wear that records your body movements. This is called an
actigraph. You should wear it all times, except in the shower or bathtub. On Day 15 (+/- 3
days), you will return the watch to the study staff and they will download information from
it.

Study Groups:

You will be randomly assigned (as in the roll of dice) to 1 of 8 study groups.

You will have an equal chance of being assigned to any group. You will have a 50% chance
(like the flip of a coin) of receiving the placebo capsule or light therapy placebo.

The skills learned during counseling will be different for each study group. The study staff
will talk to you about your assigned skills.

Neither you nor the medical study staff will know which group you are in. If needed for your
safety, the medical staff will be able to find out which group you are in.

Litebook:

All patients will use a device called a Litebook to receive either the light therapy or the
placebo light for 30 minutes within 2 hours of waking up. You will do this for 14 days. The
placebo light is not designed to have any effect on your sleep.

The Litebook is about the size of a deck of cards. To use the Litebook, you will place it on
a table within 2 feet of you while you are sitting down. You do not need to look directly
into the Litebook and you can do usual activities such as eating or reading while you are
using it. The study staff will teach you how to use the Litebook.

Study Diaries:

You will complete the following diaries at the end of each day of the 14-day study period:

- The patient diary about how much light you were exposed to using the Litebook.

- The pill diary about your medication/placebo.

It should take about 5 minutes each day to make entries in the study diaries. You will return
the diaries to the study staff at the end of the study period.

Study Drug/Placebo Administration:

You will take the methylphenidate/placebo capsule by mouth with a cup (8 ounces) of water, 2
times each day. You must take both doses before 3 PM and wait at least 2 hours between doses.
Methylphenidate may be taken without regards to meals and can be stored at room temperature.
You will also receive a copy of the FDA-approved Medication Guide specific to
methylphenidate.

You will also take the Melatonin/placebo capsule by mouth with a cup (8 ounces) of water at
bedtime.

Study Visits:

For all study visits/calls, you will be asked about any drugs you may be taking or any side
effects you may be having. At home during the study, you will continue practicing skills from
the counseling sessions and use the Litebook. You will be given a practice diary to record
practice at home, which will be reviewed at each session.

If not done at Screening, at Baseline (first visit):

- Your medical history will be recorded.

- You will have a physical exam, including measurement of your vital signs.

- You will be asked to complete the same 6 questionnaires from Screening. This should take
about 30 minutes total.

On Days 3, 8, and 15 (+/- 3 days) you will return to the clinic or be called on the phone if
you are unable to return to the clinic in person:

- You will be asked to complete a questionnaire that asks about any symptoms and/or side
effects you may be having. This should take about 10 minutes.

- You will be asked to complete 4 questionnaires. Each questionnaire should take about 5
minutes to complete, for a total of 20 minutes. The questionnaires ask about:

- Your emotional and physical well being

- Your level of fatigue

- Any anxiety and/or depression you may be having

- Any symptoms you may be having

- On Days 8 and 15 only, you will have a counselling session with a counselor either in
person or by phone. This should last about 30 minutes.

- On Day 15 only, you will complete a questionnaire about your symptoms after starting
study treatment. This should take less than 5 minutes.

Length of Study Participation:

You will take the study drug/placebo for up to 15 days (+/- 1 week) and will have a follow up
visit at Day 29 (+/- 1 week). You will no longer be able to take the study drug/placebo if
the disease gets worse, if intolerable side effects occur, if you are unable to follow study
directions, or if you cannot complete enough of the treatment combination as planned.

Your participation on the study will be over after you have completed the follow-up visit.

Follow-Up Visit:

At Day 29 (+/- 1 week) after your last dose of study drug/placebo, you will return to the
clinic for a follow-up visit.

- You will be asked about any side effects you may have had.

- You will have a physical exam, including measurement of your vital signs.

- Your performance status will be recorded.

- If not done in the past 15 days, blood (about 1 tablespoon) will be drawn for routine
tests.

- You will be asked to complete 5 questionnaires. Each questionnaire should take about 5
minutes to complete, for a total of 25 minutes. The questionnaires ask about:

- Your emotional and physical well being

- Your level of fatigue

- Any anxiety and/or depression you may be having

- Any symptoms you may be having

If you are unable to return to the clinic for the follow-up visit, the research coordinator
will call to ask about your health and you will complete the questionnaires over the phone.
This call should last about 30 minutes.

At Day 45 (+/- 5 days) or 30 days (+/- 5 days) you will receive a follow up telephone call or
return for a follow up visit to assess for side effects of the treatments.

This is an investigational study. Melatonin is an investigational drug. Melatonin is
considered a food/nutritional supplement.

The use of light therapy in patients with difficulty sleeping is investigational. It is
currently being used for research purposes only.

The combination of methylphenidate, melatonin, light therapy, and counselling for patients
with difficulty sleeping is considered investigational.

Up to 64 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients who are 18 years or older, cancer patients currently on cancer therapy with a
positive screening for SD (Screening PSQI score >/= 5).

2. Patients should have a Zubrod
3. Patients with no pain and with stable pain(defined as pain under control and on stable
doses of opioids for 1 week) are eligible.

4. Memorial delirium assessment scale
5. Controlled pain and depression symptoms, if present (defined as no change in the
Morphine equivalent dose of 30% or change in the dose of antidepressant medication in
the past 2 weeks).

6. All patients who are receiving chemotherapy and/or radiation therapy are eligible for
study if they have completed > 1 week of radiation therapy, and if they have been
approved to go on study by their primary oncologist. The PI/designated research staff
of this study will obtain and document approval from the primary oncologist and
principal investigator of the clinical trial in case the patient is on another
clinical trial as referenced in the patient's study documents.

7. Laboratory test results within these ranges: Serum creatinine bilirubin hepatic metastases are present. ULN= upper limit of normal.

8. Patients on stable doses (defined as same dose for 2 weeks) of dexamethasone,
mirtazapine, zolpidem, benzodiazepines, phenothiazines are allowed to participate in
the study.

Exclusion Criteria:

1. Have a major contraindication to methylphenidate (MP) (e.g., allergy/hypersensitivity
to study medications or their constituents), light therapy (e.g., currently receiving
UVA/UVB therapy), cognitive behavioral therapy (e.g., schizophrenia), or conditions
making adherence difficult as determined by the attending physician.

2. Currently taking MP or have taken it within the previous 10 days.

3. Patients with a diagnosis of polysomnographically confirmed obstructive sleep apnea or
narcolepsy.

4. Regularly used cognitive behavioral therapy in the last 6 weeks for sleep disturbance

5. Unable to complete the baseline assessment forms or to understand the recommendations
for participation in the study.

6. Currently with a diagnosis of major depression, manic depressive disorder,
obsessive-compulsive disorder, or schizophrenia).

7. Need monoamine oxidase inhibitors, tricyclic antidepressants, or clonidine.

8. Have glaucoma.

9. Symptomatic tachycardia and uncontrolled hypertension (determined to be clinically
significant by the PI).

10. Currently receiving anticonvulsants (phenobarbital, diphenylhydantoin, primidone),
phenylbutazone, clonidine, and/or tricyclic drugs (imipramine, clomipramine, or
desipramine).

11. Unable to speak and understand English.

12. Persons with congenital blindness and self-reported acquired blindness (independent of
the cause) with no light perception.

13. Patients with a history of retinal disease.

14. Patients with >2 hours of direct exposure to outdoor natural light per day by
interview with the Study Coordinator.

15. Patients with a diagnosis of obesity hypoventilation syndrome.

16. Positive pregnancy test for women of childbearing potential, as defined by intact
uterus and ovaries, and a history of menses within the last 12 months. Pregnancy test
to be performed no greater than 14 days prior to consent in study. In cases of women
with elevated b-HCG, these candidates will be eligible to participate so long as the
level of b-HCG is not consistent with pregnancy. Women of childbearing potential need
to be on or use contraception, or be abstinent during the study period. Their male
partners must also use contraception (condom) or maintain abstinence. Birth controls
specifications: Women who are able to become pregnant must use birth control during
the study and for 30 days after.

17. Women who are nursing.

18. Patients who have taken Melatonin within the past two weeks.