Ketamine-assisted Therapy for Advanced GI Cancer

Brief summary public domain (ClinicalTrials.gov)

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 stage 3 or 4 gastrointestinal (GI) cancers who take opioids for cancer-related pain. Advanced stage gastrointestinal (GI) cancer patients often suffer from high rates of psychosocial distress and pain. Symptoms of anxiety are highly prevalent among gastrointestinal (GI) cancers 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 cancer associated pain. GI cancer patients frequently suffer from existential distress, and demoralization is a form of existential distress that is common among people with serious medical illnesses. Demoralization 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 ketamine and talk therapy combined may improve psychosocial distress and pain, as well as decreases opioid analgesic use in patients with advanced GI cancer who take opioids for cancer-related pain.

Detailed description public domain (ClinicalTrials.gov)

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 stage 3 or 4 gastrointestinal (GI) cancers. 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 cancer 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 participants with advanced stage GI cancers 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. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.

Intervention public domain (ClinicalTrials.gov)

Drug: Ketamine. Given orally (PO)

Intervention public domain (ClinicalTrials.gov)

Drug: Ketamine Injectable Product. Given intramuscularly (IM)

Intervention public domain (ClinicalTrials.gov)

Behavioral: Meaning and Purpose therapy. In-person sessions

Intervention public domain (ClinicalTrials.gov)

Other: Placebo. Given PO or IM

Intervention public domain (ClinicalTrials.gov)

Other: Questionnaires. Questionnaires will be given over the course of the study

Arm public domain (ClinicalTrials.gov)

Blinded Group A (K-MaP) (experimental): Participants will receive 0.5mg/kg of Ketamine orally with an equivalent quantity of placebo via an intramuscular injection on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.

Arm public domain (ClinicalTrials.gov)

Blinded Group B (K-Map) (experimental): Participants will receive 0.5mg/kg of Ketamine IM with a placebo oral solution on Day 0/Visit 4 and receive Meaning and Purpose (MaP) therapy 4 times, twice before (between days -13 and -1) ketamine administration, and twice afterward on days 3 (+/- 2 days) and 11 (+/- 3 days). The duration of treatment for ketamine plus MaP (K-MaP) therapy is approximately up to 28 days. Participants will be followed up to 35 days (+/-2 days) after ketamine administration.

Primary outcome public domain (ClinicalTrials.gov)

Proportion Eligible Versus Screened Participants.. The rate of recruitment is defined as the proportion of eligible participants who participate compared to the number of total participants who were screened or signed consent but did not meet eligibility criteria will be reported. Time frame: Up to 28 days.

Primary outcome public domain (ClinicalTrials.gov)

Proportion of Participants Who Complete Therapy. Proportion of enrolled participants completing K-MaP intervention and all Demoralization Scale II (DS-II) assessments will be reported. Time frame: Up to 49 days.

Primary outcome public domain (ClinicalTrials.gov)

Frequency of Participant Responses to Intervention Acceptability. The participants will provide qualitative feedback on the acceptability of the intervention via a 20-minute interview with the study team upon study termination. Frequency of responses will be categorized and reported by arm. Time frame: 1 day.

Secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants Reporting Treatment-emergent Adverse Events. Time frame: Up to 49 days.

Secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Clinically Significant Changes in Blood Pressure. Time frame: 1 day.

Secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Clinically Significant Changes in Heart Rate. Time frame: 1 day.

Secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Challenging Experience Questionnaire (CEQ) Over Time. Time frame: 1 day.

Secondary outcome public domain (ClinicalTrials.gov)

Mean Clinician-rated Scores on the Global Clinical Impression of Severity (CGI-S) Over Time. Time frame: Up to 49 days.

Secondary outcome public domain (ClinicalTrials.gov)

Mean Clinician-rated Scores on the Demoralization Interview (DI) Over Time. Time frame: Up to 49 days.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Must have a diagnosis of a stage 3 or 4 primary GI (i.e., pancreatic, colorectal, hepatocellular, biliary, and gastro-esophageal) cancer. 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 moderate to severe demoralization as assessed by the Demoralization Scale-II (DS-II). 8. 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. Lamotrigine 2. Clozapine 3. as-needed (PRN) anxiolytics. Note: Benzodiazepine use may be allowed if used in a regular, scheduled way. Consultation with the Principal Investigator is recommended. 4. Dopamine agonists 5. Lithium 9. 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. 10. 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. 11. Must agree to the following life-style considerations: 1. Continue receiving psychotherapy or other behavioral interventions for mental health as usual. …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 1 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Slow Accrual

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Proportion Eligible Versus Screened Participants. [Up to 28 days]. Number, proportion of potential participants. Screened Participants (n=5): .60.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Proportion of Participants Who Complete Therapy [Up to 49 days]. Number, participants. Blinded Group B (K-Map) (n=1): 0.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Frequency of Participant Responses to Intervention Acceptability [1 day].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants Reporting Treatment-emergent Adverse Events [Up to 49 days]. Number, percentage of participants. Blinded Group B (K-Map) (n=1): 100.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Clinically Significant Changes in Blood Pressure [1 day]. Number, percentage of participants. Blinded Group B (K-Map) (n=1): 100.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Percentage of Participants With Clinically Significant Changes in Heart Rate [1 day]. Number, percentage of participants. Blinded Group B (K-Map) (n=1): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Challenging Experience Questionnaire (CEQ) Over Time [1 day].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Clinician-rated Scores on the Global Clinical Impression of Severity (CGI-S) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Clinician-rated Scores on the Demoralization Interview (DI) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Clinician-rated Scores on the GRID-Hamilton Depression Rating Scale (GRID-HAMD) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Proportion of Participants With Reported Demoralization Based on the Diagnostic Criteria in Psychosomatic Research (DCPR) Demoralization Scale. [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Demoralization Scale II (DS-II) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Patient Health Questionnaire 9 (PHQ-9) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Generalized Anxiety Disorder 7 (GAD-7) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Functional Assessment of Chronic Illness Therapy Palliative Care, 14 Item Version (FACIT-Pal-14) (FACIT-Pal-14) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Brief-Pain Inventory Short Form (BPI-SF) Over Time [Up to 49 days].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Proportion of Participants Reporting Any Use of Prescribed Opioids [Up to 49 days]. Number, proportion of participants. Blinded Group B (K-Map) (n=1): 1.00.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Mean Scores on the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2) [Up to 49 days].