KetaminePhase 2CIVIKNCT03362073

Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

A Phase 2 study testing Ketamine in people with Ketamine and Refractory Cancer Pain, run by Pusan National University Yangsan Hospital at 1 site in South Korea.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Ketamine, Refractory Cancer Pain
What is being tested?: Ketamine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 20 participants
Where: 1 siteSouth Korea
Study dates: 1 Jun 2018to 31 Jan 2023
Phase: Phase 2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Among patients with histologically or cytologically confirmed malignancy, patients with expected survival time of several months or less due to a progressive disease without additional anticancer treatment.
Patients with refractory cancer pain, which cases of requesting 4 or more breakthrough analgesics or increase of baseline analgesics (average pain score ≥ 4 or Personalized pain goal) in spite of 120 mg/day or more of intravenous Morphine Equivalent Daily Dose
Hospitalized patients with intravascular access during at least 5 days
Age 18 or older
Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed about all pertinent aspects of the trial prior to enrollment

Who cannot join

Patients who were treated with ketamine for pain control within 6 months
Patients who have been treated with radiotherapy within 4 weeks or plan to intervention for pain control during study period
Cancer pain cannot be excluded the Opioid induced hyperalgesia
Concomitant severe medical, surgical, or disease or problems which were contraindicated to application of Ketamine or have possibilities of unexpected medical problems caused be the Ketamine
confirmed or assumed central nervous system lesion which lead to increased intracranial pressure
Arrhythmia (supra-ventricular tachycardia, ventricular arrhythmia (frequent premature ventricular contraction, bigeminy, Ventricular tachycardia)
history of hemorrhagic stroke or seizure within 3 months

Trial locations and contacts

1 site in 1 country.

South Korea1 site

Pusan National University Yangsan Hospital
Yangsan, Gyeongsangnam-do, 50612

Other trials in South Korea

About this study

Official title: A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients With Refractory Cancer Pain

To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine

Read the detailed description

There are approximately 20 percent patients of refractory cancer pain, which is troubled with uncontrolled pain though treatment including opioids.
Ketamine has been showed the performance of Ketamine, N-methyl-D-aspartate (NMDA) receptor blocker, in refractory cancer pain based on prior studies.
We cannot yet confirm the role of Ketamine comparing the benefit and risk due to incompatible results of prior studies. Additionally, most of prior studies were studied in heterogenous groups, which are from beginning of palliative chemotherapy to terminal status, so role of ketamine was not assessed in homogeneous terminally ill cancer patients. And they has used mostly 'bolus intravenous infusion' or 'continuous subcutaneous infusion (CSCI)', relatively rare in continuous intravenous infusion (CIVI).
The bolus intravenous method is convenient but is concerned with leading to relatively severe adverse events due to poor general condition of terminally ill cancer patients, the CSCI method is not recommended because of adverse events (AEs) such as skin irritation. On the contrary, the CIVI method using gradual increasing ketamine minimizes AEs and is free of skin irritation. Most of hospitalized terminally ill cancer patients has proper IV access using intravascular devices (chemoport or PICC). So, CIVI method is suitable to hospitalized terminally ill cancer patients.
This study assess the efficacy and safety of 5-days CIVI gradual dose titration of Ketamine in terminally ill cancer patients with refractory cancer pain.

Conditions: Ketamine, Refractory Cancer Pain
Being tested: Ketamine
Keywords: Ketamine, Refractory cancer pain, Terminally ill cancer patients, Palliative care
Medical subject headings: Cancer Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
Application of ketamine using continuous intravenous infusion method during 5 days
- Ketamine 100mg/2ml + 5% Dextrose water or Normal saline 98 ml mixed fluid
- Dose schedule: 0.05mg/kg/hr -> 0.10mg/kg/hr -> … -> 0.5mg/kg/hr (increase dose at a rate of 0.05mg/kg/hr every 8 hours)

Study groups in NCT03362073
Study group	Role	What they receive
Ketamine	Experimental	continuous intravenous infusion of ketamine Receives: Drug: Ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall response rate
complete pain response plus partial pain response
- Complete pain response is defined as patient reported pain score using numerical rating scale (range 1-10) ≤ 3 or ≤ personalized pain goal (PPG) and receiving less than four rescue analgesic doses for 24 hours, without unacceptable toxicities
- Partial pain response is defined as receiving less than four rescue analgesic doses per day without a patient reported pain score using numerical rating scale (range 1-10) ≤ 3 or ≤ personalized pain goal for 24 hr, without unacceptable toxicities
Measured: From date of enrollment until 5 days or drop-out, assess up to 2 years

Secondary outcomes (7)

Change of pain intensity
Delineate changes of pain intensity daily, from the time baseline until 5th days after application of ketamine.
Pain intensity is defined as the mean of terdiurnal checked patient reported pain score during a day.
Measured: From date of enrollment until 5 days or drop-out, assess up to 2 years
Rescue analgesics for breakthrough pain
Dose and number of rescue analgesics for breakthrough pain
Measured: From date of enrollment until 5 days or drop-out, assess up to 2 years
Patient's satisfaction about Ketamine by a newly developed question in this study
Satisfaction about pain control and Ketamine-related distress during application of ketamine was evaluated by questions as follows: "How do you feel satisfaction about ketamine?" (at 5th days or drop-out)
Measured: at the 5th days or drop-out, assess up to 2 years
Guardian's satisfaction about Ketamine by a newly developed question in this study
Satisfaction about pain control and Ketamine-related distress during application of ketamine was evaluated by questions as follows: "How do you feel satisfaction about ketamine?" (at 5th days or drop-out)
Measured: at the 5th days or drop-out, assess up to 2 years
Rate of Ketamine-related adverse events
Rate of Ketamine-related adverse events
Measured: From date of enrollment until 5 days or drop-out, assess up to 2 years
Rate of early discontinuation
Rate of discontinuation due to Ketamine related AEs
Measured: From date of enrollment until 5 days or drop-out, assess up to 2 years
Overall survival
Time from application of ketamine until death or discharge/transfer
Measured: From date of enrollment until death or discharge/transfer, assess up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 201831 Jan 2023

First posted5 Dec 2017
Study start1 Jun 2018
Primary completion31 Jan 2023
Study completion31 Jan 2023

Why it stopped: The study was terminated early due to the principal investigator's transition to another institution.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (8)Papers the sponsor has linked to this study.
Other trials for KetamineStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Prospective, Single institution, Open-label, Phase 2
Masking: None (open label)
Enrolment: 20 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03362073
Sponsor's protocol ID: CIVIK
Acronym: CIVIK
Status last verified: Sep 2026
First submitted: 15 Nov 2017
Last updated: 18 Sep 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 Sep;18(9):1437-49. doi: 10.1093/annonc/mdm056. Epub 2007 Mar 12.
PubMed 17355955
Zech DFJ, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain. 1995 Oct;63(1):65-76. doi: 10.1016/0304-3959(95)00017-M.
PubMed 8577492
Hanks GW, Justins DM. Cancer pain: management. Lancet. 1992 Apr 25;339(8800):1031-6. doi: 10.1016/0140-6736(92)90546-f. No abstract available.
PubMed 1349061
Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M, Spruyt O, Rowett D, Currow DC. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 2012 Oct 10;30(29):3611-7. doi: 10.1200/JCO.2012.42.1081. Epub 2012 Sep 10.
PubMed 22965960
Jackson K, Ashby M, Martin P, Pisasale M, Brumley D, Hayes B. "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage. 2001 Oct;22(4):834-42. doi: 10.1016/s0885-3924(01)00340-2.
PubMed 11576800
Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage. 2000 Oct;20(4):246-52. doi: 10.1016/s0885-3924(00)00194-9.
PubMed 11027905
Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2017 Jun 28;6(6):CD003351. doi: 10.1002/14651858.CD003351.pub3.
PubMed 28657160
Park K, Kim JJ, Oh SB, Oh SY, Hong YJ, Kim SJ, Park EJ, Choi N, Shin SH, Kim S, Ko H. A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial). Am J Hosp Palliat Care. 2025 Mar;42(3):244-252. doi: 10.1177/10499091241252977. Epub 2024 May 16.
PubMed 38752431

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
RecruitingPhase 1
Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery
Pain, Postpartum Depression
RecruitingPhase 2
Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement
Opioid Use Disorder
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant

All Ketamine trials

Study at a glance

From the registry record, last updated by the sponsor on 18 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients With Refractory Cancer Pain
ClinicalTrials.gov ID: NCT03362073
Acronym / sponsor ID: CIVIK / CIVIK
Conditions: Ketamine, Refractory Cancer Pain
Keywords: Ketamine, Refractory cancer pain, Terminally ill cancer patients, Palliative care
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated early due to the principal investigator's transition to another institution.
Enrolment: 20 participants (actual)
Lead sponsor: Pusan National University Yangsan HospitalUniversity, hospital or other
Study start: 1 Jun 2018 (actual)
Primary completion: 31 Jan 2023 (actual)
Study completion: 31 Jan 2023 (actual)
First posted: 5 Dec 2017 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine

Detailed description

There are approximately 20 percent patients of refractory cancer pain, which is troubled with uncontrolled pain though treatment including opioids.
Ketamine has been showed the performance of Ketamine, N-methyl-D-aspartate (NMDA) receptor blocker, in refractory cancer pain based on prior studies.
We cannot yet confirm the role of Ketamine comparing the benefit and risk due to incompatible results of prior studies. Additionally, most of prior studies were studied in heterogenous groups, which are from beginning of palliative chemotherapy to terminal status, so role of ketamine was not assessed in homogeneous terminally ill cancer patients. And they has used mostly 'bolus intravenous infusion' or 'continuous subcutaneous infusion (CSCI)', relatively rare in continuous intravenous infusion (CIVI).
The bolus intravenous method is convenient but is concerned with leading to relatively severe adverse events due to poor general condition of terminally ill cancer patients, the CSCI method is not recommended because of adverse events (AEs) such as skin irritation. On the contrary, the CIVI method using gradual increasing ketamine minimizes AEs and is free of skin irritation. Most of hospitalized terminally ill cancer patients has proper IV access using intravascular devices (chemoport or PICC). So, CIVI method is suitable to hospitalized terminally ill cancer patients.
This study assess the efficacy and safety of 5-days CIVI gradual dose titration of Ketamine in terminally ill cancer patients with refractory cancer pain.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Prospective, Single institution, Open-label, Phase 2

Arm	Type	Receives
Ketamine	Experimental	Drug: Ketaminecontinuous intravenous infusion of ketamine

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Among patients with histologically or cytologically confirmed malignancy, patients with expected survival time of several months or less due to a progressive disease without additional anticancer treatment.
Patients with refractory cancer pain, which cases of requesting 4 or more breakthrough analgesics or increase of baseline analgesics (average pain score ≥ 4 or Personalized pain goal) in spite of 120 mg/day or more of intravenous Morphine Equivalent Daily Dose
Hospitalized patients with intravascular access during at least 5 days
Age 18 or older
Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed about all pertinent aspects of the trial prior to enrollment

Key exclusion criteria (7 listed)

Patients who were treated with ketamine for pain control within 6 months
Patients who have been treated with radiotherapy within 4 weeks or plan to intervention for pain control during study period
Cancer pain cannot be excluded the Opioid induced hyperalgesia
Concomitant severe medical, surgical, or disease or problems which were contraindicated to application of Ketamine or have possibilities of unexpected medical problems caused be the Ketamine

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
KetamineApplication of ketamine using continuous intravenous infusion method during 5 days * Ketamine 100mg/2ml + 5% Dextrose water or Normal saline 98 ml mixed fluid * Dose schedule: 0.05mg/kg/hr -> 0.10mg/kg/hr -> … -> 0.5mg/kg/hr (increase dose at a rate of 0.05mg/kg/hr every 8 hours)	Drug	Ketamine

Primary outcome

Overall response rate
Time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years
complete pain response plus partial pain response * Complete pain response is defined as patient reported pain score using numerical rating scale (range 1-10) ≤ 3 or ≤ personalized pain goal (PPG) and receiving less than four rescue analgesic doses for 24 hours, without unacceptable toxicities * Partial pain response is defined as receiving less than four rescue analgesic doses per day without a patient reported pain score using numerical rating scale (range 1-10) ≤ 3 or ≤ personalized pain goal for 24 hr, without unacceptable toxicities

7 secondary outcomes

Change of pain intensity
Time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years
Rescue analgesics for breakthrough pain
Time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years
Patient's satisfaction about Ketamine by a newly developed question in this study
Time frame: at the 5th days or drop-out, assess up to 2 years
Guardian's satisfaction about Ketamine by a newly developed question in this study
Time frame: at the 5th days or drop-out, assess up to 2 years
Rate of Ketamine-related adverse events
Time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years
Rate of early discontinuation
Time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years
Overall survival
Time frame: From date of enrollment until death or discharge/transfer, assess up to 2 years

Results and safety

The study was stopped early (reason given: The study was terminated early due to the principal investigator's transition to another institution.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2026.
Results publication: PubMed 17355955van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Prevalence of pain in patients with cancer: a systematic review of the past 40 years. Ann Oncol. 2007 Sep;18(9):1437-49. doi: 10.1093/annonc/mdm056. Epub 2007 Mar 12.
Results publication: PubMed 8577492Zech DFJ, Grond S, Lynch J, Hertel D, Lehmann KA. Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain. 1995 Oct;63(1):65-76. doi: 10.1016/0304-3959(95)00017-M.
Results publication: PubMed 1349061Hanks GW, Justins DM. Cancer pain: management. Lancet. 1992 Apr 25;339(8800):1031-6. doi: 10.1016/0140-6736(92)90546-f. No abstract available.
Results publication: PubMed 22965960Hardy J, Quinn S, Fazekas B, Plummer J, Eckermann S, Agar M, Spruyt O, Rowett D, Currow DC. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. J Clin Oncol. 2012 Oct 10;30(29):3611-7. doi: 10.1200/JCO.2012.42.1081. Epub 2012 Sep 10.
Results publication: PubMed 11576800Jackson K, Ashby M, Martin P, Pisasale M, Brumley D, Hayes B. "Burst" ketamine for refractory cancer pain: an open-label audit of 39 patients. J Pain Symptom Manage. 2001 Oct;22(4):834-42. doi: 10.1016/s0885-3924(01)00340-2.
Results publication: PubMed 11027905Mercadante S, Arcuri E, Tirelli W, Casuccio A. Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study. J Pain Symptom Manage. 2000 Oct;20(4):246-52. doi: 10.1016/s0885-3924(00)00194-9.
Results publication: PubMed 28657160Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst Rev. 2017 Jun 28;6(6):CD003351. doi: 10.1002/14651858.CD003351.pub3.
Derived from this study: PubMed 38752431Park K, Kim JJ, Oh SB, Oh SY, Hong YJ, Kim SJ, Park EJ, Choi N, Shin SH, Kim S, Ko H. A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial). Am J Hosp Palliat Care. 2025 Mar;42(3):244-252. doi: 10.1177/10499091241252977. Epub 2024 May 16.
Individual participant dataSharing planned: No

Related trials for Ketamine

RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
RecruitingPhase 1
Ketamine Pharmacokinetics and Pharmacodynamics for Postpartum Depression and Pain After Cesarean Delivery
Pain, Postpartum Depression
RecruitingPhase 2
Targeting Treatment-Resistant OUD With Ketamine-Assisted Mindfulness Oriented Recovery Enhancement
Opioid Use Disorder
RecruitingPhase 2
ACP-211 Monotherapy for Major Depressive Disorder With Inadequate Antidepressant Response
Major Depressive Disorder (MDD), Depressive Disorder, Treatment-Resistant

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Kwonoh Park, MD, PhD principal investigator

Pusan National University Yangsan Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ketamine in people with Ketamine and Refractory Cancer Pain, run by Pusan National University Yangsan Hospital at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The study was terminated early due to the principal investigator's transition to another institution.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (time frame: From date of enrollment until 5 days or drop-out, assess up to 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03362073, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.