Ketamine-assisted Therapy for Advanced GI Cancer

NCT06077487 | Terminated Phase 4 Results DMC FDA Drug

• 2 other identifiers: 238011NCI-2023-07386
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Pancreatic Ductal Adenocarcinoma; Pain, Acute; Gastrointestinal Cancers; Demoralization

Keywords

Medication assisted therapy; ketamine

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 28 days

• 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.

  Up to 49 days

• 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.

  1 day

Secondary Outcomes (15)

• Percentage of Participants Reporting Treatment-emergent Adverse Events

  Up to 49 days

• Percentage of Participants With Clinically Significant Changes in Blood Pressure

  1 day

• Percentage of Participants With Clinically Significant Changes in Heart Rate

  1 day

• Mean Scores on the Challenging Experience Questionnaire (CEQ) Over Time

  1 day

• Mean Clinician-rated Scores on the Global Clinical Impression of Severity (CGI-S) Over Time

  Up to 49 days

Study Arms (2)

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.

Drug: Ketamine; Behavioral: Meaning and Purpose therapy; Other: Placebo; Other: Questionnaires

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.

Drug: Ketamine Injectable Product; Behavioral: Meaning and Purpose therapy; Other: Placebo; Other: Questionnaires

Interventions

Ketamine DRUG

Given orally (PO)

Also known as: Ketalar, Ketalar Hydrocholoride

Blinded Group A (K-MaP)

Ketamine Injectable Product DRUG

Given intramuscularly (IM)

Also known as: Ketalar, Ketalar Hydrocholoride

Blinded Group B (K-Map)

Meaning and Purpose therapy BEHAVIORAL

In-person sessions

Also known as: MaP, MaP therapy, Psychotherapy

Blinded Group A (K-MaP); Blinded Group B (K-Map)

Placebo OTHER

Given PO or IM

Blinded Group A (K-MaP); Blinded Group B (K-Map)

Questionnaires OTHER

Questionnaires will be given over the course of the study

Blinded Group A (K-MaP); Blinded Group B (K-Map)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have a diagnosis of a stage 3 or 4 primary GI (i.e., pancreatic, colorectal, hepatocellular, biliary, and gastro-esophageal) cancer.
• 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.
• Must be 18 years or older.
• Must speak English and/or Spanish
• Must have a Palliative Performance Score (PPS) v. 2.0 greater than or equal to 40%.
• Must be able to swallow liquid oral medication.
• Clinically significant moderate to severe demoralization as assessed by the Demoralization Scale-II (DS-II).
• 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):
• Lamotrigine
• Clozapine
• as-needed (PRN) anxiolytics. Note: Benzodiazepine use may be allowed if used in a regular, scheduled way. Consultation with the Principal Investigator is recommended.
• Dopamine agonists
• Lithium
• 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.
• 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:

You may not qualify if:

• Has a known allergic or severe reactions to the non-psychoactive components of liquid ketamine.
• Has received treatment with another investigational drug or intervention within 1 month of signing Informed Consent Form (ICF).
• Is deemed by clinical judgment of the study investigators to be unsafe for undergoing the intervention.
• Recent use of ketamine for non-anesthesia purposes.
• Frequent use of ketamine over lifetime.
• Has a history of intra-cerebral hemorrhage.
• Has cognitive impairment sufficient to impede the ability to complete study tasks.
• Has had delirium/encephalopathy within 3 months of signing ICF.
• Has a history of intracranial hemorrhage.
• Has had a stroke (embolic) within 12 months of signing ICF.
• Has had a seizure within 6 months of signing ICF.
• Currently has an intracranial mass (e.g., primary tumor or brain metastasis).
• Has an advanced stage of a neurologic disease that puts participants at elevated risk for psychosis (e.g., Parkinson or Huntington disease).
• 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)).
• Has a history of dissociative disorder.

Sponsors & Collaborators

• Brian Anderson, MD: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Acute Pain; Gastrointestinal Neoplasms

Interventions

Ketamine; Psychotherapy; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Behavioral Disciplines and Activities; Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Limitations and Caveats

The study was terminated after one accrual due to slow accrual.

Results Point of Contact

• Title: Dr. Brian Anderson
• Organization: University of California, San Francisco

Brian.Anderson@ucsf.edu

(415) 476-1000

Study Officials

• Brian T Anderson, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study is double-blinded, meaning neither the study participants nor the study investigators will know which ketamine administration each participant is receiving.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 5, 2023
• First Posted: October 11, 2023
• Study Start: May 17, 2024
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: May 21, 2025
• Results First Posted: May 21, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)