Study of Oral Ketamine Versus Placebo for Treating Depression in Patients Undergoing Treatment for Cancer

This is a prospective, single center, double blind, randomized, two-arm feasibility study of
oral ketamine versus placebo for the treatment of depression in depressed patients with
cancer undergoing curative intent cancer therapy. Approximately 20 patients with cancer about
to undergo cancer therapy will be randomized 1:1 to receive study treatment with one of the
following regimens:

Arm A: nightly oral administration of 1.0 mg/kg ketamine Arm B: nightly oral administration
of placebo (after completion of Arm B, patients will have the option to receive a nightly
oral administration of 1.0 mg/kg ketamine and follow study procedures over again)

Consenting patients will undergo screening procedures, and if eligible, a baseline interview
and brief questionnaires regarding depression, mental and emotional health, and quality of
life assessments.

Study treatment will be administered for 12 weeks unless the patient experiences unacceptable
toxicities, exhibits moderate to severe depressive symptoms, or withdraws consent. Patients
on the placebo treatment arm will have the option to receive ketamine and follow all study
procedures over again with the ketamine drug after completion of the placebo treatment.

Patients will be asked to complete psychosocial measurements every two weeks while on study
treatment and monthly during a five-month follow-up period.

Inclusion Criteria:

- Ability to understand and the willingness to sign a written informed consent.

- Subject receiving or within twelve weeks of having received curative intent cancer
treatment with radiation and/or chemotherapy

- Age ≥ 18 years.

- Has moderate to severe depression according to Quick Inventory of Depressive
Symptomatology-Self Rated 16 (QIDS-SR-16) scores of ≥ 11 AND a Hospital Anxiety and
Depression Scale (HADS) Depression subscale score of ≥ 8.

- Documented adequate liver function within the screening period as defined by:

- ALT < 5 X institutional upper limit of normal (ULN)

- AST < 5 X institutional ULN

- Total bilirubin < 5 X institutional ULN

- Both men and women of all races and ethnic groups are eligible for this trial.

- Use of other antidepressants is permitted if dose has been the same for at least 12
weeks prior to study entry and still meet inclusion #4.

- Women of child-bearing potential and men with partners of child-bearing potential must
agree to use adequate contraception (hormonal or barrier method of birth control;
abstinence) prior to study entry and for the duration of study participation. Should a
woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her treating and the study physician immediately. Urine pregnancy
testing will be done throughout the trial for women of childbearing potential.

- Must read and understand English fluently.

Exclusion Criteria:

- Receiving another investigational agent on a clinical trial that prohibits
participation in other studies of investigational agents.

- Meets MINI International Neuropsychiatric Interview (MINI Plus), criteria for
diagnoses of schizophrenia, bipolar illness, delirium or psychosis.

- Has high Suicidal Risk Assessment (SRA) scores ≥ 10.

- Use of monoamine oxidase inhibitors within 14 days of study entry.

- History of allergic reactions or hypersensitivity to ketamine.

- Documented history of severe cardiac insufficiency (NYHA III or IV), with uncontrolled
and/or unstable cardiac or coronary artery disease.

- Documented history of significant tachyarrhythmia, severe angina, or myocardial
ischemia

- Documented history of poorly controlled hypertension (Systolic Blood Pressure > 180
mmHG or Diastolic Blood Pressure > 100 mmHG), with or without antihypertensives.

- If a woman is or becomes pregnant or is nursing at any time before or during the
treatment period, she will be excluded from the study.

- Score of ≥ 8 on the WHO Alcohol Use Disorders Identification Test (AUDIT)