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

The study is a multicenter, open-label Phase 1b single dose escalation safety study for adult subjects with intractable pain associated with cancer in any area below the mid-thoracic level who meet all other eligibility criteria.

All subjects who received RTX will be included in the analyses and summaries of safety, efficacy, PD, and PK assessments.

Inclusion Criteria:

• Histologically confirmed advanced cancer or metastasis, which has not responded to standard therapy, producing intractable chronic pain in any area below the mid-thoracic level.
• Male or female subjects must be at least 18 years of age.
• Must have a worst pain score ≥6 on the NPRS at Screening visit.
• Subjects not seeking or receiving potentially curative therapies for cancer. Palliative therapy is acceptable if the therapy started and is stable prior to IP administration.
• Sexually active female subjects of childbearing potential and male subjects capable of fathering a child must be willing to use an effective method of contraception to avoid pregnancies.
• Must be willing and capable of understanding and cooperating with the requirements of the study.
• Must be able to understand and complete study-related forms and adequately communicate with the investigator and/or site staff.
• Must have provided written informed consent prior to participating in any study-related activity.
• Subjects able to complete the study duration.

Exclusion Criteria:

• Subjects with leptomeningeal metastases in lumbar area.
• Undergoing or have plans to undergo changes to current cancer treatment during the study through the Day15 assessment.
• Had prior lumbar spine surgical procedures that could impair the ability to perform the injection.
• Evidence of brain pathology or increase intracranial pressure.
• Presence of an IT shunt.
• Has evidence or a coagulopathy or hemostasis problem.
• Subjects with a total neutrophil count <1500 cells/mm3.
• Subjects with serum creatinine ≥1.5 mg/dL.
• Is febrile or has other evidence of an infection within 7 days of planned injection.
• Has an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic contrast agents.
• Female subjects who are pregnant, are planning on becoming pregnant, or are currently breastfeeding.
• Subjects with any medical condition that could adversely impact study participation or assessments.
• Subjects who have received new anti-cancer treatments and there is less than one week or four half-lives of the investigational drug, whichever is greater, between the last dose of the new drug and the planned day of IP administration; or had a change in the dose or schedule of the anti-cancer treatments within one week or four half-lives, whichever is greater, between the last dose of the anti-cancer treatment and the planned day of IP administration; or are scheduled to receive a new anti-cancer therapy or investigational product prior to completion of the Day 15 visit.
• Subjects with additional loci of pain above the mid-thoracic level or other pain disorder due to non-cancer etiology, unless both the investigator and the subject are clearly able to distinguish the additional pain from the target pain due to cancer.
• Liver cirrhosis or severe hepatic impairment, with liver function test 3 times above ULN.
• Sensory/peripheral neuropathy of CTCAE Grade 2 or higher.
• Nonstudy related minor surgical procedure ≤5 days or major surgical procedure ≤21 days prior to Screening visit.
• Subjects who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies that are CTCAE Grade 3 or higher.
• Arterial thrombi (including stroke), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within 3 months prior to Screening visit.
• Corrected QT using Fridericia's formula (QTcF) prolongation.
• Evidence or history of bleeding disorder within 4 weeks prior to IP administration.
• Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.