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

A Randomized, Double Blind, Feasibility Study of Oral Ketamine Versus Placebo for Prevention of Depression in Patients Undergoing Treatment for Pancreatic or Head and Neck Cancers

The primary purpose of this study is to see if it is safe to give patients with pancreatic or head and neck cancer a low dose of the FDA approved anesthetic drug ketamine at the same time they receive radiation and/or chemotherapy for their cancer treatment to prevent depression and its effects. Researchers would also like to see if giving ketamine at the same time as cancer treatment is practical and reasonably acceptable to the patient.

New onset depression is highly frequent in those with head and neck cancer, and depression has many negative consequences for outcomes in those patients. Depression has been known to have greater incidence in pancreatic cancer patients than in patients with other malignancies.

Therefore, investigators would also like to see if giving patients ketamine during their routine cancer treatment will prevent the onset of depression and its negative effects on cancer treatment outcomes, and also help with anxiety, pain, and quality of life. The study will also use a placebo to compare to the good and/or bad effects of ketamine. A placebo is not an active drug and it will be look the same as ketamine, as a liquid to be taken by mouth.

Ketamine is approved by the U.S. Food and Drug Administration (FDA) as a general anesthetic by itself for some diagnostic and surgical procedures or combined with other general anesthetic agents. It has also been shown to reduce cancer pain. Ketamine is considered experimental in this study because it is not approved by the FDA for the prevention of depression.

Study Overview

• Status: Withdrawn
• Conditions: Depression; Head and Neck Cancer; Pancreatic Cancer
• Intervention / Treatment: Drug: Ketamine; Other: Placebo

Detailed Description

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.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketamine; oral ketamine 0.5 mg/kg mixed with syrup	Drug: Ketamine; Ketamine 0.5 mg/kg mixed with syrup will be given by mouth once a week for 12 weeks.; Other Names: Ketalar
Placebo Comparator: Placebo; oral placebo (syrup)	Other: Placebo; Placebo syrup will be given by mouth once a week for 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients pre-screened that were potentially eligible for study participation.		36 months
Proportion of patients that were potentially eligible who were approached.		36 months
Proportion of approached patients that decline study participation and why.		36 months
Proportion of approached patients that agreed to participate.		36 months
Proportion of approached that were randomized.		36 months
Proportion of patients discontinuing prematurely from study treatment for any reason, including side effects attributed to ketamine or side effects attributed to placebo, documenting reasons for dropout.		36 months
Proportion of patients that are evaluable	Subjects with a baseline and one post-baseline visit are evaluable and will be included in the analyses.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related adverse events	Adverse Events rated as possibly/probably related to study treatment	4 months
Patient-reported tolerability questionnaire (FIBSER)		4 months
Treatment expectancy and satisfaction as measured by the credibility/expectancy questionnaire (CEQ).		4 months

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of new onset mild, moderate, or severe depressive symptoms as assessed by questionnaire (QIDS-SR-16)	4 months
Depression-free survival	4 months
Severity of cancer-related pain as assessed by a visual analog scale (VAS)	4 months
Anxiety and depressive symptoms as assessed by questionnaire (HADS)	4 months
Quality of life as assessed by questionnaire (UW-QOL)	4 months
Suicide risk and ideation as assessed by questionnaire (SRA)	4 months

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Scott Irwin, MD, PhD, Cedars-Sinal Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2016
• Primary Completion (Actual): November 3, 2017
• Study Completion (Actual): November 3, 2017

Study Registration Dates

• First Submitted: May 7, 2015
• First Submitted That Met QC Criteria: May 12, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Actual): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 2, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Ketamine; Prevention of depression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Neoplasms; Neoplasms by Site; Depression; Depressive Disorder; Head and Neck Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: IIT2015-22-IRWIN-KETPREVE; 1R21CA197023-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No