Ketamine for Preventing Depression in Patients Undergoing Treatment for Pancreatic or Head and Neck Cancers

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

- Arm A: weekly oral administration of 0.5 mg/kg ketamine

- Arm B: weekly oral administration of placebo

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 not be eligible to cross over to the ketamine arm at
evidence of depression but will be removed from the study and treated with standard medical
management for depression.

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

Inclusion Criteria:

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

2. Stage -II-IV epidermoid cancer of the head and neck OR stage III-IV pancreatic cancer,
with prognosis of at least three months, per oncologist.

3. Within two weeks of starting or from having started, curative intent therapy for head
and neck cancer.

4. Age ≥ 18 years.

5. Adequate liver function as defined by:

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

- AST < 5 X institutional ULN

- Total bilirubin < 5 X institutional ULN

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

7. Use of antidepressants is permitted if dose has been the same for at least 12 weeks
prior to study entry if patient still DOES NOT meet exclusion criteria #3.

8. 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 the study team and her treating physician immediately. Urine
pregnancy testing will be done throughout the trial for women of childbearing
potential.

9. Must read and understand English fluently.

Exclusion Criteria:

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

2. Meets Mini International Neuropsychiatric interview (MINI) criteria for major
depression, schizophrenia, bipolar illness, delirium or psychosis.

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

4. Has Suicidal Risk Assessment (SRA) scores ≥ 6.

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

6. Diagnosed with melanoma or lymphoma cancer of the head and neck.

7. Diagnosed with Stage I or II pancreatic cancer or with anticipated survival of less
than three months.

8. History of allergic reactions or hypersensitivity to ketamine.

9. Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable
cardiac or coronary artery disease.

10. History of significant tachyarrhythmia, severe angina, or myocardial ischemia

11. Poorly controlled hypertension (Systolic Blood Pressure > 180 mmHG or Diastolic Blood
Pressure > 100 mmHG), with or without antihypertensives.

12. 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.

13. Score of ≥ 8 on the WHO Alcohol Use Disorders Identification Test (AUDIT, sensitivity
of 0.8).