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

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)