Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the flip of a coin) to 1 of 2 study groups:

- If you are in Group 1, you will receive lorazepam.

- If you are in Group 2, you will receive a placebo.

Neither you nor the study staff will know if you are receiving the study drug or the placebo.
However, if needed for your safety, the study staff will be able to find out what you are
receiving. You will have an equal chance of being in each group.

All patients will receive haloperidol as part of your standard of care. The study doctor can
tell you more about haloperidol, how it is designed to work, and about any side effects it
may have.

Study Drug Administration:

After you have started receiving haloperidol, you will receive lorazepam or the placebo by
vein 1 time over about 1-2 minutes.

Study Tests:

Every day while you are in the palliative care unit, you will be asked to complete the same
questionnaires about symptoms and how you are feeling that you were asked at screening. If at
any point you recover from your confusion, you will be asked if you remember the confusion
and how distressing it was.

Saliva Samples:

While you are in the hospital, saliva samples (about 1/2 a teaspoon) will be collected every
day to check for changes in your body's chemical levels. To collect the saliva, a swab will
be brushed inside your mouth until enough saliva is gathered on the swab. This should take
about 30 seconds to complete.

Length of Study:

You will receive the study drug or placebo 1 time. You will be monitored as part of this
study until you leave the palliative care unit. You may go off study at any time that
you/your caregiver decides it is in your best interest.

This is an investigational study. Lorazepam is FDA approved and commercially available for
the treatment of anxiety, insomnia, and seizures. Its use to help control agitation/delirium
is investigational.

Up to 60 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. [Patients] Diagnosis of advanced cancer (defined as locally advanced, metastatic,
recurrent, or incurable disease)

2. [Patients] Admitted to Acute Palliative Care Unit (APCU)

3. [Patients] Delirium as per the Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV-TR) criteria

4. [Patients] Hyperactive/mixed delirium with RASS >/=2 in the last 24 hours

5. [Patients] On scheduled haloperidol of
6. [Patients] Age 18 or older

7. [Patients] Legally Authorized Representative consent

8. [Family Caregivers] Patient's spouse, adult child, sibling, parent, other relative, or
significant other (defined by the patient as a partner)

9. [Family Caregivers] Age 18 or older

10. [Family Caregivers] At the patient's bedside at least 4 hours each day during patient
delirium episode

11. [Patients and Family Caregivers] Able to communicate in English or Spanish

Exclusion Criteria:

1. [Patients] History of myasthenia gravis or acute narrow angle glaucoma

2. [Patients] History of neuroleptic malignant syndrome

3. [Patients] History of Parkinson's disease or dementia

4. [Patients] Uncontrolled seizure disorder

5. [Patients] History of hypersensitivity to haloperidol or benzodiazepine

6. [Patients] On regular doses of benzodiazepine or chlorpromazine within the past 48
hours

7. [Patients] Previously documented and persistent QTc prolongation (>500 ms)

8. [Patients] Heart failure exacerbation at the time of enrollment