Epidural injection of 1.5mL/min RTX under the guidance of epidurogram.

Intractable Cancer Pain

single dose (0.4, 1, 2, 4, 8,15, 25 or 35 mcg), epidural injection

Resiniferatoxin

University of Miami/Sylvester Comprehensive Cancer Center

Brigham & Women's Hospital

Duke University Medical Center

Hermann Drive Surgical Hospital

Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain

A Multicenter, Open-Label, Phase 1b Study to Assess the Safety and Define the Maximally Tolerated Dose of Epidural Resiniferatoxin Injection for the Treatment of Intractable Pain Associated With Cancer

Grade 3 or 4 Toxicity associated with RTX administration

Maximum dose without a Grade 3 or 4 toxicity

Daily average pain and daily worst pain on a 0-10 scale

Consumption of analgesics compared to baseline

Quality of life compared to baseline by the total score

Patient-reported rating of improvement on a 7-point scale, ranking the improvement from (1) to (7), with (1) being no change or worse to (7) being a great deal better and a considerable improvement that has made all the difference.

A 11-point scale for rating average and worst pain at the location intended to be treated with RTX within 12 hours of the clinical visit, with 0 being no pain to 10 being worst pain imaginable.

Quality of life affected by pain at the location intended to be treated with RTX, each question rates pain level and pain interference on a 0 to 10 scale. For pain level questions, 0 represents no pain and 10 represents pain as bad as can be imagined. For pain interference questions, 0 is "does not interfere" and 10 is "completely interferes".

Sorrento Therapeutics, Inc.

The design uses a traditional "3+3" rule-based design that does not stipulate any prior assumption of the dose-toxicity curve. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.

Schedule a maximum of 3 periganglionic DRG injection(s) at contiguous level(s) to treat targetedDRG responsible for chronic CIBP

Intractable Pain

Palliative Care

Resiniferatoxin (RTX) is an ultrapotent agonist analog of capsaicin that targets a receptor expressed on specific dorsal root sensory ganglia (DRG) neurons and is expected to reduce pain within the targeted zone.

National Institutes of Health Clinical Center, 9000 Rockville Pike

Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

An Open-Label, Phase 1b Safety and Efficacy Trial of Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-Induced Bone Pain

MTD will be defined as 1 dose level below that at which dose-limiting toxicity (DLT) is observed in more than one third of the subjects.

The Investigator will assess the AE for severity and relationship of the AE to RTX or the injection (causality determination of the AE toeither the RTX or the injection procedure itself).

DLT is defined as the development in a subject of a CTCAE grade 3 or higher agent-related toxicity or two or more grade 2 agentrelatedtoxicities occurring in the same subject at any time from dosing through the D14 visit.

The average of the daily worst NRS scores will be used throughout the study for post-injection visits.

The BPI is a validated tool designed to assess the severity of pain and the impact of pain on daily functions in patients with cancer pain and pain due to other chronic diseases.

National Institute of Neurological Disorders and Stroke (NINDS)

phase I, single-site, non-randomized, open-label, dose- escalation study to determine the safety and efficacy of IT RTX in subjects with severe refractory pain due to advanced malignancy

Intrathecal Resiniferatoxin

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer

Dose escalation decisions are based on both effectiveness (as assessed by mean worst pain on the NRS) and DLT. The dose escalation population will include all subjects who are dosed, complete the NRS, and have the DLT assessments from baseline through Day 15. Subjects who are not evaluable for dose escalation will be replaced.

The secondary outcome variables will be summarized over time by dose cohort as appropriate for the outcome measure. Absolute and percentage change in the NRS and VAS pain scores between the pre- and post-RTX dosing assessments (baseline period and study Days 8 through 14, respectively) will also be summarized.

resiniferatoxin/rak

Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain

Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

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