Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer
This study will examine the safety of giving the experimental drug, resiniferatoxin (RTX), to treat severe pain in patients with advanced cancer. RTX is a chemical extracted from a cactus-like plant. It is similar to capsaicin, the active ingredient in hot pepper. RTX has relieved pain and reduced the need for pain medication in several animal experiments. It works by destroying nerves that transmit pain information.
People 18 years of age with severe pain from advanced cancer that cannot be controlled with standard treatments may be eligible for this study. Participants undergo the following procedures:
Before beginning treatment with RTX, patients give a medical history and undergo a physical examination that includes:
- Electrocardiogram (EKG)
- Blood draw
- Eye examination
- Pregnancy test, when appropriate
Questionnaires to collect information on health, personality, mood, pain levels and symptoms.
Patients are hospitalized for 2 days for RTX injection and monitoring, as follows:
- RTX injection: RTX is injected in the operating room under general anesthesia. It is given through a catheter placed in the patient s spine. The catheter is also used to obtain samples of cerebrospinal fluid (CSF) the clear fluid that bathes the spinal cord. The fluid is examined to assess drug effects and side effects, chemical changes in the content of the CSF associated with RTX, and how RTX is handled by the body.
- Post-injection monitoring, including:
- Surveys about symptoms such as pain or weakness
- Neurological examinations
- Blood and CSF sampling
(The first two patients enrolled in the study are hospitalized for 4 days and receive two injections: a very low dose of drug on day 1 and a higher, potentially more effective dose on day 3. Some of the examinations, questionnaires and CSF sampling are repeated after the second injection.)
- Blood draw, neurological and sensory testing, EKG on days 7, 14 and 30 after the injection
- MRI scans of the head and back on day 14 after the injection
- Eye examination
- Follow-up phone calls monthly for 6 months
Drug: Intrathecal Resiniferatoxin
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer|
- Phase I trial to demonstrate the safety of administering resiniferatoxin (RTX) directly into the human CNS (fluid bathing the spinal cord). [ Time Frame: 6 months from treatment ] [ Designated as safety issue: Yes ]
- Confirm that injection of RTX in CNS has pain-relieving properties (analgesia) resulting in lower pain scores, improvements in quality of life, and possibly opoid sparing properites in patients with refractory pain. [ Time Frame: 6 months from treatment ] [ Designated as safety issue: No ]
|Study Start Date:||December 2008|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Pain continues to be a major problem in patients with advanced cancer. Resiniferatoxin (RTX), a potent member of the family of drugs that includes capsaicin, selectively and irreversibly destroys the neurons (or their axons) transmitting chronic pain sensation. Intrathecal injection of RTX in several animal species has demonstrated a high level of safety, specificity, and efficacy in treating severe pain. This first-in-human, dose-escalation study will investigate the intrathecal administration of RTX in cancer patients with severe pain.
To investigate the safety and efficacy of RTX administered intrathecally in subjects with severe refractory pain associated with advanced cancer.
Up to 45 subjects will be accrued as described in Section 8.5. Eligible subjects will be greater than or equal to 18 years of age, have a clinical and histological diagnosis of advanced malignancy, and have severe pain due to malignancy that is at or below the level of the chest and not adequately relieved by other pain control therapies.
This will be a single-site, non-randomized, open-label, dose-escalation study using a modified Fibonacci scheme. The starting dose of RTX will be 13 micro g. Doses will then be increased in progressively smaller percentage increments. Dose escalation will occur in sequential groups of 3 subjects until 1 escalation above the effective dose in 100% of subjects (ED100), completion of the 166 mirco g dose level, or establishment of the maximum tolerated dose (MTD), whichever occurs first. The total duration of study participation for any subject will be up to 7 months.
The primary study outcome is the ED100, the MTD, or the maximum dose administered, whichever is achieved first during dose escalation. The primary pain variable for determining the ED100 is the daily worst pain score averaged over a 7-day period during the 3 weeks before RTX dosing and during Days 8 through 14 after dosing. The numerical rating scale (NRS), administered verbally during a daily telephone interview, will be the primary pain assessment instrument. For a given subject, the treatment will be considered effective if the subject experiences a greater than or equal to 50% reduction in the mean daily worst pain score assessed by NRS.
Secondary outcome measures will be other surveys of pain, including an assessment of worst daily pain by the visual analog scale, and assessments of function and quality of life.
Safety assessments will include hematology; serum clinical chemistry tests; cerebrospinal fluid examinations; physical, neurological, and eye examinations; reporting of adverse events; electrocardiograms; and findings of magnetic resonance imaging of the spine and brain.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00804154
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||John D Heiss, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|