Oral Ketamine for Anxiety in Pancreatic Cancer Patients

Overseen By Ana V Martin, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Cedars-Sinai Medical Center

Must be taking: Antidepressants

Must not be taking: MAOIs

Disqualifiers: Schizophrenia, Bipolar, Severe cardiac, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 10 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how oral ketamine might reduce anxiety in people with pancreatic cancer. Researchers aim to assess patient adherence to the treatment plan and compare the safety and tolerability of ketamine to a placebo. The study will also explore the treatment's effects on depression, anxiety, and pain. Participants must have a pancreatic cancer diagnosis and experience moderate to severe anxiety while undergoing or having recently completed cancer treatment. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial allows participants to continue using standard antidepressants for anxiety if the dose has been stable for at least 12 weeks before joining the study. However, you cannot have taken a monoamine oxidase inhibitor (MAOI) within 14 days of starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ketamine is generally safe. Doctors have used it as an anesthetic in hospitals for a long time. While most people tolerate ketamine well, some may experience "emergence reactions," which are psychological effects like vivid dreams or confusion, occurring in about 12% of patients. Some find these effects pleasant, while others do not.

Ketamine has been tested in various situations, and even accidental overdoses have been managed without major issues. However, this study is in the early stages, focusing primarily on assessing the treatment's safety. This step is crucial as it helps researchers understand how people might react to ketamine when used for anxiety in pancreatic cancer patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anxiety in pancreatic cancer patients?

Unlike the standard treatments for anxiety in pancreatic cancer, which often include medications like benzodiazepines and antidepressants, oral ketamine offers a novel approach with a potentially rapid effect. Ketamine is unique because it targets the brain's NMDA receptors, which is different from the traditional anxiety medications that usually impact serotonin or GABA pathways. Researchers are excited about ketamine because it can provide quick relief from anxiety symptoms, possibly within hours or days, compared to the weeks it often takes for other medications to become effective. Additionally, its oral administration makes it convenient and accessible for patients undergoing cancer treatment.

What evidence suggests that this treatment might be an effective treatment for anxiety in pancreatic cancer patients?

Research has shown that ketamine may help reduce anxiety and depression. In a 28-day study with hospice patients, taking ketamine orally each day significantly improved their depression and anxiety. Other studies have found that low doses of ketamine can help with depression in cancer patients. This trial will explore ketamine's effects on anxiety in pancreatic cancer patients. Participants will receive either ketamine followed by a placebo or a placebo followed by ketamine, with each treatment phase lasting 4 weeks and separated by a washout period. While more research is needed, these early results are promising for its potential use. ^{6 7 8 9 10}

Who Is on the Research Team?

Scott Irwin, MD, PhD

Principal Investigator

Cedars-Sinai Medical Center

Are You a Good Fit for This Trial?

Adults with pancreatic cancer and moderate to severe anxiety, currently or recently treated for cancer, can join. They must understand English, agree to use contraception if needed, avoid alcohol and driving post-medication. Those on stable antidepressants may qualify but not if they have certain psychiatric conditions, high suicide risk, ketamine allergy, severe heart issues or uncontrolled blood pressure.

Inclusion Criteria

Agrees to abstain from alcohol use while taking study medication

My liver is functioning well, as confirmed by recent tests.

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

Exclusion Criteria

My blood pressure has been over 180/100 twice in the last two months.

Refusal/inability to comply with inclusion criterion #10 (driving restrictions) and inclusion criterion #11 (alcohol abstinence) during study treatment period

I haven't taken MAOI drugs in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly oral administration of 0.5mg/kg ketamine or placebo for 4 weeks, followed by a crossover to the alternate treatment for another 4 weeks, separated by a 2-week washout period

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketamine
• Placebo

Trial Overview This study tests oral ketamine against a placebo in reducing anxiety among pancreatic cancer patients. It's a double-blind trial where neither the participants nor the researchers know who gets what treatment until after the results are collected. The effects on mood, physical function and inflammation markers will be measured.

How Is the Trial Designed?

Group I: Arm B: Placebo Followed by Ketamine Experimental Treatment 2 Interventions

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).

Group II: Arm A: Ketamine Followed by Placebo Experimental Treatment 2 Interventions

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).

Ketamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in European Union as Ketalar for:

• Anesthesia
• Treatment-resistant depression

Approved in United States as Spravato for:

• Treatment-resistant depression

Approved in European Union as Spravato for:

• Treatment-resistant depression

Approved in Canada as Spravato for:

• Treatment-resistant depression

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Published Research Related to This Trial

In a 28-day open-label trial with 14 hospice patients, daily oral ketamine significantly improved symptoms of depression and anxiety, with all subjects responding positively by the end of the study.

The improvements in depressive symptoms were noticeable by day 14, while anxiety symptoms showed significant response as early as day 3, and side effects were minimal, primarily consisting of diarrhea and sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily oral ketamine for the treatment of depression and anxiety in patients receiving hospice care: a 28-day open-label proof-of-concept trial. Irwin, SA., Iglewicz, A., Nelesen, RA., et al.[2023]

Oral ketamine is a potentially safe and effective treatment for depression, but it requires higher doses (2.0-2.5 mg/kg) compared to intravenous administration due to lower systemic absorption (20%-25%).

Despite its promise as a more accessible and affordable option for treatment, the current literature on oral ketamine is limited, and further research is needed to understand its pharmacokinetics, safety, and efficacy compared to other administration routes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 2: Practical Considerations. Andrade, C.[2020]

In a study of 201 adults with treatment-resistant major depressive disorder (MDD) or bipolar disorder (BD), intravenous (IV) ketamine significantly reduced symptoms of anxiety, irritability, and agitation in those with mixed features, indicating its effectiveness in treating these symptoms.

Participants with anxiety, irritability, and agitation (AIA) experienced greater reductions in overall depressive symptoms and suicidal ideation compared to those without AIA, suggesting that IV ketamine could be a rapid treatment option for adults with mood disorders presenting with mixed features.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of ketamine on anxiety, irritability, and agitation: Implications for treating mixed features in adults with major depressive or bipolar disorder. McIntyre, RS., Lipsitz, O., Rodrigues, NB., et al.[2021]

Ketamine and MK 801 were found to significantly increase the migration of pancreatic cancer cells by promoting the expression of the integrin beta-3 receptor, which is associated with tumor progression and metastasis.

Understanding how perioperative medications like ketamine affect cancer cell behavior is crucial for developing targeted therapies, highlighting the need for further research into the mechanisms of pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta-3-mediated Cell Migration in Pancreatic Carcinoma. Malsy, M., Hofer, V., Schmidbauer, S., et al.[2023]

A case series involving three hospice patients demonstrated that a single subcutaneous dose of ketamine (0.5 mg/kg) followed by daily oral ketamine (0.5 mg/kg) led to rapid improvement in depression symptoms, as measured by various assessment tools.

This approach offers a potentially effective and convenient method for managing depression in hospice patients, providing quicker relief compared to traditional antidepressant therapies, although further prospective studies are needed to optimize dosing strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Subcutaneous Ketamine Dose Followed by Oral Ketamine for Depression Symptoms in Hospice Patients: A Case Series. Latuga, NM., Luczkiewicz, DL., Grant, PC., et al.[2021]

A case report on a 44-year-old hospice patient showed that a single low-dose subcutaneous injection of ketamine (0.5 mg/kg) provided significant relief from severe anxiety, chronic pain, and depression for up to 80 hours, demonstrating its efficacy in palliative care.

The patient continued to experience symptom relief with a daily compounded flavored oral ketamine solution, indicating that ketamine can be effectively administered in a home-based setting for patients with multiple comorbid conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compounded oral ketamine. McNulty, JP., Hahn, K.[2013]

A recent randomized controlled trial found that subcutaneous ketamine does not provide a clinical benefit over placebo for managing cancer pain that does not respond to other treatments, leading to significant changes in clinical practice among Australasian clinicians.

Following the trial, 65% of surveyed clinicians altered their prescribing habits for ketamine, with many prescribing it less frequently or only in specific situations, reflecting a shift in practice based on the trial's findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. Hardy, JR., Spruyt, O., Quinn, SJ., et al.[2015]

Oral ketamine has shown effectiveness in treating severe depression, including treatment-resistant cases and those with suicidal ideation, based on various studies including randomized controlled trials with doses ranging from 0.25 to 7 mg/kg.

Despite its lower bioavailability (20%-25% reaching the bloodstream), oral ketamine is well tolerated and can be adjusted for individual needs, making it a practical option for depression treatment alongside conventional antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ketamine for Depression, 1: Pharmacologic Considerations and Clinical Evidence. Andrade, C.[2019]

In a study of 417 cervical carcinoma patients with mild to moderate depression, high-dose S-ketamine (0.5 mg/kg) significantly reduced pain and depression scores compared to control and other treatment groups at 1 and 3 days post-surgery.

Both low-dose (0.25 mg/kg) and high-dose S-ketamine improved short-term outcomes better than racemic ketamine, with increased serum levels of BDNF and 5-HT, indicating a potential mechanism for its efficacy in managing depression and pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Various Doses of S-Ketamine in Treatment of Depression and Pain in Cervical Carcinoma Patients with Mild/Moderate Depression After Laparoscopic Total Hysterectomy. Wang, J., Wang, Y., Xu, X., et al.[2021]

A Phase I study involving 32 patients showed that esketamine (0.5 mg/kg) is generally safe and well-tolerated for use in painless gastroscopy, with no serious adverse events reported.

Esketamine resulted in a shorter recovery time compared to racemic ketamine (9 minutes vs. 13 minutes), making it a potentially more efficient option for anesthesia without gender differences affecting its pharmacokinetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Esketamine in Chinese Patients Undergoing Painless Gastroscopy in Comparison with Ketamine: A Randomized, Open-Label Clinical Study. Wang, J., Huang, J., Yang, S., et al.[2022]

In two reported cases, a single oral dose of ketamine provided rapid and moderately sustained relief from depression and anxiety in hospice patients, suggesting its potential effectiveness in this setting.

No adverse effects were noted with the use of ketamine, indicating it may be a safe treatment option, but further randomized controlled trials are needed to confirm its efficacy and safety for hospice care patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care. Irwin, SA., Iglewicz, A.[2021]

Citations

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Feasibility Study of Oral Ketamine Versus Placebo for the ... To investigate the tolerability of oral ketamine in patients with pancreatic cancer and anxiety, which will be measured by patient-reported Ketamine Adverse ...

2. withpower.com withpower.com/trial/early-phase-1-pancreatic-neoplasms-11-2021-9de98

Oral Ketamine for Anxiety in Pancreatic Cancer Patients In a 28-day open-label trial with 14 hospice patients, daily oral ketamine significantly improved symptoms of depression and anxiety, with all subjects ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10764987/

The efficacy and safety of ketamine for depression in patients ... Included studies showed administration of sub-anesthesia ketamine significantly improves postoperative depression among patients with cancer.

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SAFETY DATA SHEET VetaKet® (ketamine hydrochloride injection, USP) ... Occupational Safety and Health. Administration (OSHA):. Not considered to be a carcinogen.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf

KETALAR (ketamine hydrochloride) injection Ketamine has a wide margin of safety; several instances of unintentional administration of overdoses of. KETALAR (up to ten times that usually required) have ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2012/016812s039lbl.pdf

Ketalar Label - accessdata.fda.gov SPECIAL NOTE. EMERGENCE REACTIONS HAVE OCCURRED IN APPROXIMATELY 12 PERCENT OF PATIENTS. THE PSYCHOLOGICAL MANIFESTATIONS VARY IN SEVERITY BETWEEN PLEASANT ...

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Label: KETASET- ketamine hydrochloride injection - DailyMed To report suspected adverse reactions, to obtain a Material Safety Data Sheet or for technical assistance, call 1-888-963-8471. Close. ACTION. KETASET is a ...

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Label: KETALAR- ketamine hydrochloride injection - DailyMed KETALAR should be administered by or under the direction of physicians experienced in the administration of general anesthetics, maintenance of a patent airway, ...