Trial Title:
Ketamine-assisted Therapy for Patients With Pancreatic Ductal Adenocarcinoma
NCT ID:
NCT06077487
Condition:
Pancreatic Ductal Adenocarcinoma
Pain, Acute
Conditions: Official terms:
Adenocarcinoma
Ketamine
Conditions: Keywords:
Medication assisted therapy
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Triple (Participant, Care Provider, Investigator)
Masking description:
The study is double-blinded, meaning neither the study participants nor the study
investigators will know which ketamine administration each participant is receiving.
Intervention:
Intervention type:
Drug
Intervention name:
Ketamine
Description:
Given orally (PO)
Arm group label:
Group A (K-MaP)
Other name:
Ketalar
Other name:
Ketalar Hydrocholoride
Intervention type:
Drug
Intervention name:
Ketamine Injectable Product
Description:
Given intramuscularly (IM)
Arm group label:
Group B (K-Map)
Other name:
Ketalar
Other name:
Ketalar Hydrocholoride
Intervention type:
Behavioral
Intervention name:
Meaning and Purpose therapy
Description:
In-person sessions
Arm group label:
Group A (K-MaP)
Arm group label:
Group B (K-Map)
Other name:
MaP
Other name:
MaP therapy
Other name:
Psychotherapy
Intervention type:
Other
Intervention name:
Placebo
Description:
Given PO or IM
Arm group label:
Group A (K-MaP)
Arm group label:
Group B (K-Map)
Summary:
This clinical trial evaluates whether it is possible to use a single dose of ketamine in
combination with talk therapy to treat moderate to severe demoralization in patients with
pancreatic ductal adenocarcinoma (PDAC) who take opioids for cancer-related pain. PDAC
patients often suffer from high rates of psychosocial distress and pain. Symptoms of
anxiety are highly prevalent among PDAC patients. While opioid analgesia (pain reliever)
succeeds in managing some symptoms, chronic opioid therapy is associated with significant
adverse effects, underscoring a need to identify alternative interventions in the
treatment of PDAC-associated pain. PDAC patients frequently suffer from existential
distress. Demoralization is a form of existential distress that is common among people
with serious medical illnesses; it is characterized by poor coping with stressful events,
and a loss of meaning and purpose in life. Talk therapy is a form of psychological
treatment during which patients discuss problems, thoughts, and feelings. Ketamine has
demonstrated efficacy for the treatment of depression, suicidality, and pain in
non-cancer patients. This study may help researchers learn whether both ketamine and talk
therapy may improve psychosocial distress and pain, as well as decreases in opioid
analgesic use in patients with PDAC who take opioids for cancer-related pain.
Detailed description:
PRIMARY OUTCOMES:
I. To assess the feasibility of Meaning and Purpose therapy combined with oral ketamine
(K-MaP) in demoralized participants.
SECONDARY OUTCOMES:
I. To characterize the preliminary safety and tolerability of K-MaP in demoralized
participants with pancreatic ductal adenocarcinoma.
II. To assess the magnitude and durability of improvement from randomization in
psychosocial distress.
III. To assess the magnitude and durability of improvement from randomization in pain.
IV. To assess the magnitude of change from randomization in opioid analgesic use.
V. To assess the magnitude and durability of change from randomization in interoceptive
awareness
EXPLORATORY OBJECTIVES:
I. To assess how the participant's subjective experiences with ketamine may be related to
clinical outcomes.
II. To assess how participants' stage of PDAC may be related to clinical outcomes.
III. To assess how the participants' changes in measures of cardiac interoception
following receipt of ketamine may be related to subjective experiences with ketamine and
clinical outcomes.
OUTLINE:
Adult pancreatic ductal adenocarcinoma (PDAC) participants receiving care at the Helen
Diller Family Comprehensive Cancer Center (HDFCCC) will be randomized in a 1:1 ratio to
one of two double-blinded conditions consisting of a single drug treatment and several
therapy sessions, for up to 7 weeks. Participants will be followed up to 35 days (+/-2
days) after ketamine administration.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Must have a diagnosis of pancreatic ductal adenocarcinoma (PDAC) of any stage.
2. Must be willing to sign the informed consent form (ICF) and follow the study
procedures as outlined in the ICF for the duration of the study.
3. Must be 18 years or older.
4. Must speak English and/or Spanish
5. Must have a Palliative Performance Score (PPS) v. 2.0 greater than or equal to 40%.
6. Must be able to swallow liquid oral medication.
7. Clinically significant demoralization as assessed by the Demoralization Scale-II
(DS-II).
8. Must have used any opioid-based analgesia for cancer-related pain in the last 7 days
(at time of screening).
9. Must discontinue the following medications and refrain from taking following
medications for the duration of study participation (participants who require these
medications will be taken off study):
1. Antipsychotics
2. as-needed (PRN) anxiolytics. Note: Benzodiazepine use may be allowed if used in
a regular, scheduled way. Consultation with the Principal Investigator is
recommended.
3. Dopamine agonists
4. Lithium
10. Female-born participants of child-bearing potential with male-born partners must use
highly effective contraception for at least 1 month prior to ketamine administration
(on day 0) and agree to use such a method for an additional 2 months after ketamine
administration.
11. Male-born participants with female-born partners of child-bearing potential must use
highly effective contraception for at least 1 month prior to ketamine administration
and agree to use such a method for an additional 2 months after ketamine
administration. Note: Highly effective contraception include:
- Intrauterine device (IUD)
- Intrauterine hormone-releasing system (IUS)
- Non-oral hormonal methods, including injected, intravaginal, implanted,
transdermal
- Oral hormones plus a barrier contraception (condom, diaphragm, or spermicide)
- Double barrier method (at least two of the following: condom, diaphragm, and
spermicide)
- Vasectomy
- Abstinence from penile-vaginal intercourse* *The reliability of abstinence
should be evaluated carefully with the participant in relation to their general
lifestyle. An additional acceptable birth control method should be discussed
with the participant in case participants decide to engage in penile-vaginal
intercourse during the course of the study.
12. Must agree to the following life-style considerations:
1. Continue receiving psychotherapy or other behavioral interventions for mental
health as usual. Current interventions should not be stopped and new
interventions should not be started during the study period once participants
are enrolled in the study.
2. Consume no more than a modest quantity (e.g., 1 cup) of caffeine or
xanthine-containing products (e.g., coffee or tea) the morning of receiving
ketamine (on Day 0/Visit 4).
3. Abstain from alcohol for 24 hours before receiving ketamine.
4. Abstain from using any nicotine-containing products (including nicotine
patches) for 3 hours before receiving ketamine.
5. If cannabis products are used regularly, participants will be asked to continue
using regular amount, but will be asked not to use cannabis within 24 hours
prior to receiving ketamine.
6. If prescribed a regular dose of benzodiazepines, participants will be asked not
to take medication the morning of the ketamine administration visit.
7. If taking any psychostimulants (e.g., methylphenidate), participants will be
asked not to take psychostimulant drugs (other than caffeine) the morning of
the ketamine administration visit.
8. Will be advised to maintain their usual opioid regimen.
Note: Input will be obtained from the participant's regular clinical providers on
appropriate pain management for the participant during the study, particularly in the
case of analgesics associated with adverse reactions of concern with ketamine (e.g.,
tramadol and any opioid may increase risk of respiratory depression from ketamine).
Exclusion Criteria:
1. Has a known allergic or severe reactions to the non-psychoactive components of
liquid ketamine.
2. Has received treatment with another investigational drug or intervention within 1
month of signing Informed Consent Form (ICF).
3. Is deemed by clinical judgment of the study investigators to be unsafe for
undergoing the intervention.
4. Has used ketamine within 5 years of signing ICF. Note: Ketamine used for anesthesia
for medical procedures is permissible.
5. Has a lifetime use of ketamine for non-anesthetic purposes ≥10 times.
6. Has a history of intra-cerebral hemorrhage.
7. Has cognitive impairment sufficient to impede the ability to complete study tasks.
8. Has had delirium/encephalopathy within 3 months of signing ICF.
9. Has a history of intracranial hemorrhage.
10. Has had a stroke (embolic) within 12 months of signing ICF.
11. Has had a seizure within 6 months of signing ICF.
12. Currently has an intracranial mass (e.g., primary tumor or brain metastasis).
13. Has an advanced stage of a neurologic disease that puts participants at elevated
risk for psychosis (e.g., Parkinson or Huntington disease).
14. Has a history of a primary psychotic disorder or primary bipolar disorder I or II
(determined by Quick Structured Clinical Interview for Diagnostic and Statistical
Manual version 5 Disorders (QuickSCID-5)).
15. Has a history of dissociative disorder.
16. Recent, clinically significant suicidal ideation. Note: This does not include
requesting medical aid in dying.
17. Is currently receiving electroconvulsive therapy (ECT), transcranial magnetic
stimulation (TMS) or similar somatic therapies.
18. Has baseline hypertension (≥140 SBP or ≥90 DBP), after repeated measurements. Note:
Participants with hypertension that has been controlled by medication down to <140
Systolic blood pressure (SBP) and <90 diastolic blood pressure (DBP) will be allowed
participate.
19. Has a history of aneurysmal vascular disease or dissection (including thoracic and
abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous
malformation.
20. Has had cardiac arrest within 12 months of signing ICF.
21. Has had a myocardial infarction within 12 months of signing ICF.
22. Has QTcf >450msec on 12-lead EKG. Note: Participants may qualify for the study if
QTc 450-480 msec on one EKG, but then <=450 msec on repeat EKG taken >1 day later.
If QT-prolonging medications are started or increased in dose after enrollment and
prior to ketamine administration, a repeat EKG must be done >12-hours after this
change in order to assure continued safe enrollment in the trial.
23. Has clinically significant arrhythmia defined as
1. Ventricular fibrillation or ventricular tachycardia within 1 year of signing
ICF
2. Bradycardia, severe, within 1 year of signing ICF Note: Participants with
pacemakers will be considered to be eligible at the discretion of the Principal
Investigator.
3. Atrial fibrillation, continuous
4. Atrial fibrillation, intermittent, without rate or rhythm control
5. Supraventricular tachycardia (SVT), without standard treatment
6. Other clinically significant arrhythmias (e.g., Wolf Parkinson White)
24. Has symptomatic congestive heart failure (NYHA Class II-IV)
25. Has severe obstructive intracardiac abnormalities (e.g., aortic stenosis)
26. Has any current condition where physical activity is associated with palpitations,
anginal pain or syncope.
27. Is unable to protect their own airway due to dysphagia, difficulty swallowing or a
neurologic disease resulting in a risk of aspiration.
28. Has a history of flash pulmonary edema within 12 months of signing ICF.
29. Has a diagnosis of moderate or severe pulmonary hypertension.
30. Needs supplemental oxygen (intermittent or continuous).
31. Has current intractable nausea/vomiting/diarrhea.
32. Has had a clinically significant GI bleed within 6 months of signing ICF.
33. Meets the following laboratory parameters:
1. Asymptomatic alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
>=5x upper limit of normal (ULN).
2. Symptomatic ALT or AST >= 2x ULN.
3. Total bilirubin > 2x ULN (Gilbert syndrome is allowed)
4. Alkaline phosphatase >5x ULN
5. International Normalized Ratio (INR) > 3.0
6. Renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) < 30
milliliter/minute (mL/min) /1.73 m^2 (using the 2021 Chronic Kidney Disease
Epidemiology Collaboration (CKD-EPI) Creatinine Equation), Creatinine Clearance
(CrCl) < 30 mL/min (using the Cockcroft-Gault Equation), or current dialysis)).
34. Is currently pregnant or breastfeeding.
35. Has insulin-dependent diabetes with diabetes-related hospitalization within 6 months
of signing ICF.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
Zoe Lopez-Meraz
Email:
Ketamine-PDAC@ucsf.edu
Contact backup:
Phone:
877-827-3222
Email:
cancertrials@ucsf.edu
Investigator:
Last name:
Brian T Anderson, MD
Email:
Principal Investigator
Investigator:
Last name:
Andrea Rosati, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Nicky Mehtani, MD, MPH
Email:
Sub-Investigator
Start date:
May 17, 2024
Completion date:
December 31, 2024
Lead sponsor:
Agency:
Brian Anderson, MD
Agency class:
Other
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06077487
