Feasibility Study of Oral Ketamine Versus Placebo for the Treatment of Anxiety in Patients With Pancreatic Cancer

• ClinicalTrials.gov Identifier: NCT05086250
• Recruitment Status: Suspended
• First Posted: October 20, 2021
• Last Update Posted: April 18, 2023
• Sponsor: Cedars-Sinai Medical Center
• Information provided by (Responsible Party): Scott A. Irwin, MD, PhD, Cedars-Sinai Medical Center

Study Description

Brief Summary:

This is a prospective, single center, double blind, randomized, crossover feasibility study of oral ketamine versus placebo for the treatment of anxiety in patients with pancreatic cancer currently receiving or within 12 weeks of receiving cancer targeted therapy. The primary objective is to determine the feasibility of enrolling subjects and treatment adherence. The secondary objectives are to describe the safety and tolerability. Exploratory objectives are to assess the effect of ketamine/placebo on Depression, Anxiety, Physical Function, Pain Interference, Pain Intensity, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities as measured by PROMIS Anxiety Short Form 7a and the PROMIS-29 Profile v2.1 of Patient Reported Outcomes, as well as changes in circulatory inflammatory cytokines, blood glutamine levels, and other biomarkers of anxiety and/or depression.

Condition or disease	Intervention/treatment	Phase
Anxiety; Pancreatic Cancer	Drug: Ketamine; Drug: Placebo	Early Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)

Masking Description

Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or subjects. The following study procedures will be in place to ensure double-blind administration of study treatments.

• Access to the randomization code will be strictly controlled
• Packaging and labeling of test and control treatments will be identical to maintain the blind The research pharmacist will manage the investigational agent. The blind will be maintained through the effort of the research pharmacist and the pharmacy. Unblinding will only occur when it is deemed medically necessary. The date and reason for breaking the blind will be documented.

• Primary Purpose: Supportive Care
• Official Title: A Prospective, Single Center, Double Blind, Randomized, Crossover Feasibility Study of Oral Ketamine Versus Placebo for the Treatment of Anxiety in Patients With Pancreatic Cancer
• Actual Study Start Date: October 20, 2022
• Estimated Primary Completion Date: September 2023
• Estimated Study Completion Date: December 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: Ketamine Followed by Placebo; Weekly oral administration of 0.5mg/kg ketamine for 4 weeks, followed by weekly oral administration of placebo for 4 weeks (separated by a washout period of 2 weeks).	Drug: Ketamine; Weekly oral administration of 0.5mg/kg ketamine for 4 weeks, followed by weekly oral administration of placebo for 4 weeks (separated by a washout period of 2 weeks).; Other Name: Ketalar; Drug: Placebo; Weekly oral administration of 0.5mg/kg ketamine for 4 weeks, followed by weekly oral administration of placebo for 4 weeks (separated by a washout period of 2 weeks).
Experimental: Arm B: Placebo Followed by Ketamine; Weekly oral administration of placebo for 4 weeks, followed by weekly oral administration of 0.5mg/kg ketamine for 4 weeks (separated by a washout period of 2 weeks).	Drug: Placebo; Weekly oral administration of placebo for 4 weeks, followed by weekly oral administration of 0.5mg/kg ketamine for 4 weeks (separated by a washout period of 2 weeks).; Drug: Ketamine; Weekly oral administration of placebo for 4 weeks, followed by weekly oral administration of 0.5mg/kg ketamine for 4 weeks (separated by a washout period of 2 weeks).; Other Name: Ketalar

Outcome Measures

Primary Outcome Measures :

1. Feasibility of enrolling subjects which will be measured by the proportion of patients dropping out of study for any reason prior to the end of treatment visit. [ Time Frame: 2 months ]

   The following will be collected as part of this feasibility measurement:

   • Reasons for dropout.
   • Proportion of patients pre-screened that were potentially eligible for study participation.
   • Proportion of patients that were potentially eligible who were approached.
   • Proportion of approached patients that decline study participation and why.
   • Proportion of approached patients that agreed to participate.
   • Proportion of approached that were randomized.
   • Proportion of patients completing study through End of Treatment visit and each follow-up visit.

Secondary Outcome Measures :

1. To investigate the safety of oral ketamine in patients with pancreatic cancer and anxiety, which will be assessed by the number of adverse events related to study treatment per CTCAE v.5. [ Time Frame: 3 months ]
   Th number of adverse events related to study treatment assessed per CTCAE v.5.
2. To investigate the tolerability of oral ketamine in patients with pancreatic cancer and anxiety, which will be measured by patient-reported Ketamine Adverse Symptom Checklist and Impact scores. [ Time Frame: 3 months ]
   This is a self-report tool that provides patient rating (none, mild, moderate, severe) of 33 potential side effects of ketamine. The Adverse Symptom Checklist (ASC) is scored 0 (none), mild (1), moderate (2), and severe (3 points). This scale also asks patients to quantify side effect interference in daily activities, also scored the same way (Min value 0, Max Value 3). Therefore, the total score for the ASC has Min value 0, Max 102 where total higher scores mean a worse outcome. The ASC responses will be dichotomized (frequency: 0%-25% vs >25%; intensity: none, mild vs moderate, or greater; burden: none to mild impairment vs moderate or greater impairment) and will be descriptively summarized by each treatment arm at each assessment time point.

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Ability to understand and the willingness to sign a written informed consent.
2. Participant has been diagnosed with pancreatic cancer.
3. Receiving or within twelve weeks of having received cancer targeted treatment, including surgery, radiation, chemotherapy, immunotherapy, or other cancer targeted therapy.
4. Age ≥ 18 years.
5. Has moderate to severe anxiety according to the PROMIS Anxiety Short Form 7a and/or PROMIS-29 anxiety module (T-score of > 60).
6. Documented adequate liver function within the screening period.
7. Use of concomitant standard antidepressants targeting anxiety (e.g. SSRIs) is permitted if dose has been the same for at least 12 weeks prior to study entry and patient still meets inclusion #5.
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 while receiving study drug. Women of child-bearing potential must have a negative urine or blood pregnancy test at screening. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician and study staff immediately.
9. Must be able to read and understand English.
10. Required not to engage in potentially hazardous activities, such as driving a motor vehicle or operating machinery, after receiving a medication dose until the next day after a restful sleep (as per recommendations with Spravato).
11. Agrees to abstain from alcohol use while taking study medication.

Exclusion Criteria:

1. Initial cancer diagnosis ≤6 weeks prior to Day 0.
2. Meets MINI International Neuropsychiatric Interview (MINI Plus), criteria for diagnoses of schizophrenia, bipolar illness, delirium or psychosis.
3. Scores ≥ 10 on the Suicidal Risk Assessment (SRA).
4. History of allergic reactions or hypersensitivity to ketamine.
5. Documented history of severe cardiac insufficiency (NYHA III or IV), with currently uncontrolled and/or unstable cardiac or coronary artery disease.
6. Current or recent significant tachyarrhythmia, severe angina, or myocardial ischemia, as assessed by a study physician.
7. Documented history of poorly controlled hypertension (Systolic Blood Pressure > 180 mmHG or Diastolic Blood Pressure > 100 mmHG twice within a one-month period in last two months), with or without antihypertensives.
8. Women who are pregnant or nursing or expect to become pregnant or start nursing during the expected trial duration, and women of childbearing potential who refuse to use contraceptives to prevent childbearing.
9. Uncontrolled hypo- or hyperthyroidism, as assessed by a study physician.
10. Diagnosis of dementia.
11. Treatment with monoamine oxidase inhibitor (MAOI) within 14 days of Day 0.
12. Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
13. History of intracerebral hemorrhage.
14. Refusal/inability to comply with inclusion criterion #10 (driving restrictions) and inclusion criterion #11 (alcohol abstinence) during study treatment period.

Contacts and Locations

Locations

United States, California

Cedars-Sinai Medical Center

Los Angeles, California, United States, 90048

Sponsors and Collaborators

Cedars-Sinai Medical Center

Investigators

• Principal Investigator: Scott Irwin, MD, PhD; Cedars-Sinai Medical Center

More Information

• Responsible Party: Scott A. Irwin, MD, PhD, Director, Patient and Family Support Program, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT05086250
• Other Study ID Numbers: IIT2019-18-IRWIN-KETANX
• First Posted: October 20, 2021
• Last Update Posted: April 18, 2023
• Last Verified: April 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Scott A. Irwin, MD, PhD, Cedars-Sinai Medical Center:

ketamine; placebo

Additional relevant MeSH terms:

Pancreatic Neoplasms; Anxiety Disorders; Mental Disorders; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Ketamine; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action