Symptoms and General Pathology

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Nervous System Diseases

Cancer Pain

Pain

Neurologic Manifestations

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Ketamine

Anesthetics

Anesthetics, Dissociative

Anesthetics, Intravenous

Anesthetics, General

Excitatory Amino Acid Antagonists

Neurotransmitter Agents

continuous intravenous infusion of ketamine

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)

Kwonoh Park, MD, PhD

Mikyung Kang

So Yeon Oh

Sang-Bo Oh

Eun-Ju Park

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

* 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.

Prospective, Single institution, Open-label, Phase 2

Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients

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

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

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.

Dose and number of rescue analgesics for breakthrough pain

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)

Rate of discontinuation due to Ketamine related AEs

Time from application of ketamine until death or discharge/transfer

Pusan National University Yangsan Hospital

Professor, clinical research

Antineoplastic Agents

Lenalidomide

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Sriram Yennurajalingam, MD

The goal of this clinical research study is to learn if lenalidomide can help to treat uncontrolled pain caused by advanced cancer.

Primary Objectives:

1. Determine efficacy of Lenalidomide for the treatment of refractory cancer pain, as measured by the change on Edmonton symptom assessment scale (ESAS).

Secondary Objectives:

1. To determine the effect of Lenalidomide on fatigue, sleep, depressed mood, nausea and appetite/anorexia.
2. Determine changes in serum levels of inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, interferon(IFN)-alpha and IFN-gamma, and C-reactive protein) before and after treatment with Lenalidomide.
3. Effect of Lenalidomide on T-cell subsets especially T-regulatory cells
4. Effect of Lenalidomide on the expression of costimulatory receptors, CD80, CD86, and CD40, on myeloid and plasmacytoid dendritic cells
5. Safety (type, frequency, severity, and relationship of adverse events to study treatment)

The Study Drug:

Lenalidomide is designed to change the body's immune system. It may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may decrease or prevent the growth of cancer cells. The drug is also designed to decrease the level of certain proteins in the blood called cytokines, which may result in decreased pain.

Study Drug Administration:

If you are found to be eligible to take part in this study, you will take lenalidomide capsules each morning, with or without food. Take lenalidomide capsules whole, with a 4-ounce (1/2 cup) glass of water at the same time each day. Do not break, chew, or open the capsules. If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you miss taking your dose for the entire day, take your regular dose the next scheduled day (do NOT take double your regular dose to make up for the missed dose).

If you take too much lenalidomide, call your study doctor or health care provider or poison control center right away.

You will also be allowed to take strong pain killers such as morphine as prescribed by your study doctor for pain. If you need more than 3 doses of these pain killers in a 24-hour period, you should call your study doctor.

Study Visits:

You will visit the clinic throughout the study. At each visit, you will be asked to return any unused study drug and empty bottles to the clinic and you will be asked about any side effects you may be experiencing. The last study visit will be on Day 43 or Day 57, depending on the side effects you may experience. The following tests and procedures will be performed:

On Day 8:

Blood (about 1 tablespoon) will be drawn for routine tests and women who are able to have children will have a blood pregnancy test.

Day 15:

Blood (about 1 tablespoon) will be drawn for routine tests. Women who are able to have children will have a blood (1-2 teaspoons) pregnancy test. You will complete 5 questionnaires about the pain, the pain symptoms, and any side effects you may be having. The questionnaires will take about 30 to 40 minutes to complete. Women who are able to have children will have a blood pregnancy test.

Day 22:

Blood (about 1 tablespoon) will be drawn for routine tests. Women who are able to have children will have a blood (1-2 teaspoons) pregnancy test.

Day 29:

You will complete the same questionnaires as on Day 15. Women who are able to have children will have a blood pregnancy test and will be counseled about pregnancy precautions and risks. Blood (about 1 tablespoon) will be drawn for routine tests. Women who are able to have children will have a blood (1-2 teaspoons) pregnancy test.

Day 36:

Blood (about 1 tablespoon) will be drawn for routine tests.

Day 43:

Blood (about 1 tablespoon) will be drawn for routine tests. You will complete the same questionnaires as on Day 15. If this is your last visit, you will have an ECG. Women who are able to have children will have a blood (1-2 teaspoons) pregnancy test.

Day 57 (if necessary):

You will complete the same questionnaires as on Day 15. Blood (about 1 tablespoon) will be drawn for routine tests. You will complete the same questionnaires as on Day 15. If this is your last visit, you will have an ECG. Women who are able to have children will have a blood (1-2 teaspoons) pregnancy test.

Day 71 (if necessary):

If you stopped taking the drug on Day 57, a blood (1-2 teaspoons) pregnancy test will be done.

Length of Study:

You may take lenalidomide for up to 57 days. You will be taken off study if the disease gets worse or if intolerable side effects occur.

If you are a female who is able to have children and you do take lenalidomide for all 57 days, you will be required to have a blood (1-2 teaspoons) pregnancy test 28 days after your last dose of lenalidomide.

The routine blood draws on Days 8, 22, and 36 may done at your home (by a study nurse), local doctor's office, or at M. D. Anderson.

All patients who were on lenalidomide and then stopped taking it, will be checked every 3 to 5 weeks for a period of 1 year. During the follow-up visits, certain tests and procedures will be performed. These include a symptom questionnaire, blood draw for routine tests, a check of your side effects, and pregnancy testing for women who are still able to become pregnant. These are the same tests that were done while you were on the study.

Daily Drug Diary and Questionnaire:

Starting on Day 1 until the end of the study, you will complete a questionnaire once daily about any symptoms and pain you may be experiencing. It will take about 5 minutes to complete each time. You will also be provided with a drug diary to write down when and how often you take pain medication. You should bring your completed diary to each study visit so it can be reviewed by the research nurse.

Phone Call Follow-up:

You will be contacted by telephone at home to be asked questions about your symptoms and any side effects you may have experienced. You will be called on Day 8 (plus or minus 3 days), Day 22 (plus or minus 3 days) and Day 36 (plus or minus 3 days). The phone calls will last about 10-15 minutes each time.

End-of-Study Visit:

You will come to the clinic 28 days after your last dose of lenalidomide for a follow-up visit. You will be checked for side effects, and women who are able to have children must have a negative blood (1-2 teaspoons) pregnancy test.

This is an investigational study. Lenalidomide is approved by FDA for the treatment of myelodysplastic syndrome (MDS) and in combination with dexamethasone for patients with multiple myeloma (MM). Lenalidomide is not FDA approved for pain relief. Its use in this study is investigational. If you experience intolerable pain after you stop receiving the study drug, you will be allowed to start receiving lenalidomide (off study). You will be monitored for side effects for every 2-3 weeks while you are on this medication for a period of 1 year. Up to 15 patients will take part in this study. All will be enrolled at M. D. Anderson.

Lenalidomide (Revlimid) for the Treatment of Refractory Cancer Pain

A Pilot Clinical Trial of Lenalidomide (Revlimid®) for the Treatment of Refractory Cancer Pain

Changes in cancer pain from baseline to day 15 using ESAS to measure participant responses to 10 common symptoms (pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep problems, and feeling of well-being). Intensity of symptoms rated on a 0 to 10 scale from 0 "no symptom" to 10 "worst possible symptom."

Celgene Corporation

M.D. Anderson Cancer Center

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Sriram Yennurajalingam, MD / Assistant Professor

Participant 1

Participant 2

One participant was not evaluable for Day 15.

Change in Cancer Pain Intensity Determined by Edmonton Symptom Assessment Scale (ESAS)

Overall Study

Channel Blockers

Anticonvulsants

Morphine

Oxcarbazepine

Analgesics, Opioid

Narcotics

Sodium Channel Blockers

Diuretics, Potassium Sparing

Patients must be on stable or increasing doses of greater than or equal to 180 mg of morphine sulfate per day. Morphine is taken orally for 42 days.

In addition to Morphine, patients will also receive oral Oxcarbazepine 150 mg, every 12 hours, for 2 weeks, then increase the dose to 300 mg, every 12 hours, for 2 weeks and then increase the dose to 450 mg, every 12 hours, for the final 2 weeks. Patients will take oral tablets of oxcarbazepine for a total of 42 days.

Morphine will be given to patients as part of their standard care

Can be taken with or without food at the same time as morphine. Morphine will be provided to patients free of charge.

Costantine Albany, M.D.

This is an open-label, single arm, Phase Ib dose escalation study of Oxcarbazepine with morphine in patients with refractory cancer pain. The primary endpoint is to evaluate the safety and toxicity of the combination of Oxcarbazepine plus morphine. The secondary endpoints are improving pain control, reduce morphine use and improve the quality of life.

Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain

A Phase Ib Study of Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain

Evaluate the safety and toxicity of oxcarbazepine in combination with morphine

Evaluate changes in pain control after adding oxcarbazepine to morphine

Evaluate changes morphine consumption after adding oxcarbazepine to morphine

Evaluate changes in Quality of Life after adding oxcarbazepine to morphine

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Continuous IntraVenous Infusion of Ketamine in Terminally Ill Cancer Patients	NCT03362073	Ketamine Refractory Canc...	Ketamine	18 Years -	Pusan National University Yangsan Hospital
Lenalidomide (Revlimid) for the Treatment of Refractory Cancer Pain	NCT00684242	Advanced Cancer Pain	Lenalidomide	18 Years -	M.D. Anderson Cancer Center
Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain	NCT02078089	Cancer	Morphine Oxcarbazepine	18 Years -	Indiana University
Oxcarbazepine Plus Morphine in Patients With Refractory Cancer Pain	NCT02078089	Cancer	Morphine Oxcarbazepine	18 Years -	Indiana University

Spots Global Cancer Trial Database for refractory cancer pain