Clinical trial NCT03146806: Intranasal (NAS) Ketamine for Cancer Pain
Official title: Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer Related Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cancer
Pain
Keywords: Cancer pain
Anesthesiology
Opiates
Intranasal ketamine
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2017-05-10
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The main purpose of this study is to determine the safety, feasibility, and utility of intranasal (NAS) ketamine in persistent uncontrolled cancer related pain. In this prospective clinical trial the researchers will investigate the use of NAS ketamine in patients with pain related to cancer or cancer treatment. The researchers plan to enroll at least 25 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the supportive oncology clinic, oncology clinics, the pain clinic and Acute Pain Service at Emory. Participants will be asked to return to the Phase I unit of the Winship Cancer Building C for a total of 5 study visits, each two to five days apart. During these visits participants will complete questionnaires, have blood samples drawn and will have study medication administered to them in escalating doses. For safety monitoring participants will be contacted by telephone 14 days after the last dose of medication administered.

Detailed description: There are about 11.9 million Americans affected with cancer. 53% of patients with cancer experience pain at all stages of cancer. These patients often require high doses of opioids with uncontrolled pain that makes them too sedated to effectively participate in day-to-day activities and have a good quality of life. Depression often co-exists with cancer pain due to the nature of the disease. The researchers are searching for improved therapies for chronic cancer pain and ketamine with its novel mechanism of action may be a promising solution.

Ketamine is an FDA approved anesthetic with the ability to effect memory loss, pain relief and sedation. Safety and efficacy of ketamine as an anesthetic and analgesic agent is well documented. Low doses of ketamine have minimal adverse impact on circulatory or breathing functions but can reduce pain. Research has shown that ketamine is effective in controlling breakthrough pain and reducing depression in a randomized double blind controlled trial. There is limited data regarding the use of ketamine for pain management in cancer.

One of the challenges with ketamine is the route of administration, most commonly given intravenously (IV) or intramuscularly (IM). It has also been given by mouth and rectally, but absorption is very poor. Intranasal (NAS) administration may be a promising method of delivery and can be ordered by a physician from a compounding pharmacy. From other research the investigators expect absorption to be higher than oral or rectal administration and this method of delivery as needle-free is a patient-friendly route of administration.

The main purpose of this study is to determine the safety, feasibility, and utility of intranasal (NAS) ketamine in persistent uncontrolled cancer related pain. In this prospective clinical trial the researchers will investigate the use of NAS ketamine in patients with pain related to cancer or cancer treatment. The researchers plan to enroll at least 15 patients meeting inclusion/exclusion criteria, to achieve a minimum of 10 patients who complete the study. Participants will be recruited from the oncology clinic, pain clinic and Acute Pain Service at Emory. Participants will be asked to return to the Phase I unit of the Winship Cancer Building C for a total of 5 study visits, each two to five days apart. During these visits participants will complete questionnaires, have blood samples drawn and will have study medication administered to them in escalating doses. For safety monitoring participants will be contacted by telephone 14 days after the last dose of medication administered.

Data obtained from this study will help determine if ketamine provides a reduction of pain using the Numeric Pain Rating Scale and a reduction in the use of opioid consumption and other rescue medications. Additionally the researchers will study the bioavailability, pharmacodynamics and pharmacokinetics of ketamine and the safety profile of NAS ketamine.

Eligibility criteria: Inclusion Criteria:

* Patients with uncontrolled pain related to cancer or cancer treatment. Uncontrolled pain will be defined as:

  * Pain which persists for more than 7 days and is rated \>/=4 on Numerical Pain Rating Score (NPRS)
  * Use of breakthrough medication more than 4 times in 24 hours or being treated with oral morphine equivalent of 50 mg/d or more
* Patients who are able to follow-up in person during the trial
* Patient on stable analgesic regimen for \>7 days without escalation during study period with rescue or immediate release medication every 3 hours or longer
* Patients who are willing and able to maintain a daily pain diary
* Patients who are able to understand written and verbal English
* Patient weight \>/= 50 kg

Exclusion Criteria:

* Transportation issues interfering with return study visits
* Patients with high disposition of laryngospasm or apnea
* Presence of severe cardiac disease
* Presence of conditions where significant elevations in blood pressure would be a serious hazard.
* Stage 2 hypertension or greater (systolic blood pressure \> 160 and/or diastolic blood pressure \>100)
* Baseline tachycardia, heart rate (HR) \>100
* History of seizures, elevated intracranial pressure (ICP) or cerebrospinal fluid (CSF) obstructive states (e.g. severe head injury, central congenital or mass lesions)
* Conditions that may increase intraocular pressure (e.g. glaucoma, acute globe injury)
* History of uncontrolled depression or other psychiatric comorbidity with psychosis
* History of liver disease
* History of interstitial cystitis
* History of nasal or sinus anomalies or dysfunction e.g. allergic or infectious rhinitis.
* Patients with lesions to the nasal mucosa
* Pregnant women, nursing mothers and women of childbearing potential not using contraception known to be highly effective. Highly effective contraception methods include combination of any two of the following:

  * Use of oral, injected or implanted hormonal methods of contraception or;
  * Placement of an intrauterine device (IUD) or intrauterine system (IUS);
  * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository;
  * Total abstinence or;
  * Male/female sterilization.
* Illicit substance abuse within the past 6 months
* Documented history of medication abuse/misuse (e.g. Unsanctioned dose escalation, broken opioid agreement etc.)
* Clinical requirement for medications that are concurrent inducers or inhibitors of CYP3A4. CYP3A4 substrates are allowed.
* Porphyria (possibility of triggering a porphyric reaction)
* Severe active anemia ( a hemoglobin\< 8 documented by labs drawn within 3 months of first study treatment)
* History of difficult intravenous access
* Intractable vomiting

Primary outcomes:
measure: Bioavailability of Ketamine
timeFrame: Baseline, Minutes 2, 30, 60, and 240 during Study Visits 1 through 4, up to 4 weeks
measure: Peak Concentration (Cmax) of Ketamine
timeFrame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks
measure: Area Under the Curve of Ketamine
timeFrame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 Weeks
measure: Time to Peak Concentration (Tmax) of Ketamine
timeFrame: Minute 2 through Minute 240 during Study Visits 1 through 4, up to 4 weeks
measure: Numerical Pain Rating Scale (NPRS) Score
timeFrame: Baseline, Minutes 5, 10, 15, 30, 45, 60, 120, 180, and 240 during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Fatigue Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Dizziness Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Nausea Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Headache Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Feeling of Unreality Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Hearing Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Change in Vision Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Mood Change Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) General Discomfort Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Side Effect Rating Scale for Dissociative Anesthetics (SERSDA) Hallucinations Score
timeFrame: Baseline, Minutes 30, 60, and 240, during Study Visits 1 through 4, up to 4 weeks
measure: Montgomery Asberg Depression Rating Scale (MADRS) Score
timeFrame: Baseline and Minute 180, during Study Visits 1 through 5, up to 6 weeks
measure: Edmonton Symptom Assessment System (ESAS) Score
timeFrame: Baseline during Study Visits 1 through 5, up to 6 weeks
measure: Eastern Cooperative Oncology Group (ECOG) Score
timeFrame: Baseline during Visits 1 through 4, up to 4 weeks
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Score
timeFrame: Baseline during Visit 1 and Visit 5, up to 6 weeks
Secondary outcomes:
measure: Frequency of Rescue Medication Use
timeFrame: Visit 1 through Visit 5, up to 6 weeks
measure: Total Opioid Consumption
timeFrame: Visit 1 through Visit 5, up to 6 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
Study officials:
affiliation: Emory University
name: Vinita Singh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shteamer JW, Harvey RD, Spektor B, Curseen K, Egan K, Chen Z, Gillespie TW, Sniecinski RM, Singh V. Safety of Intranasal Ketamine for Reducing Uncontrolled Cancer-Related Pain: Protocol of a Phase I/II Clinical Trial. JMIR Res Protoc. 2019 Apr 30;8(4):e12125. doi: 10.2196/12125.