A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer
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
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I trial to demonstrate the safety of administering resiniferatoxin (RTX) directly into the human CNS (fluid bathing the spinal cord).
6 months from treatment
John D Heiss, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
United States: Federal Government
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