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

Study Overview
=================
Brief Summary
-----------------
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.

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

Official Title
-----------------
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

Conditions
-----------------
Intractable Cancer Pain

Intervention / Treatment
-----------------
* Drug: Resiniferatoxin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RTX epidural injection<br>Epidural injection of 1.5mL/min RTX under the guidance of epidurogram. | Drug: Resiniferatoxin<br>* single dose (0.4, 1, 2, 4, 8,15, 25 or 35 mcg), epidural injection<br>* Other names: RTX;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | Grade 3 or 4 Toxicity associated with RTX administration | 3-month | 
| Maximum tolerated dose (MTD) | Maximum dose without a Grade 3 or 4 toxicity | 3-month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numeric Pain Rating Scale (NPRS) | Daily average pain and daily worst pain on a 0-10 scale | Day-28 to Day90 daily | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Resiniferatoxin, RTX, Cancer pain