Study to Assess Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer

Study Overview
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Brief Summary
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This Phase 2 study assesses the safety and efficacy of a single injection of Resiniferatoxin versus placebo for the treatment of intractable advanced cancer pain.

Detailed Description
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This is a global multicenter, randomized Phase 2 study for subjects with advanced cancer experiencing intractable pain to assess the safety and efficacy of a single epidural injection of Resiniferatoxin versus vehicle control. Additional subjects who elect to not enroll but are willing to be followed will comprise a Concurrent Control Group. Subjects will be followed for twelve months.

Official Title
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A Multicenter, Phase 2 Study to Assess the Safety and Efficacy of Epidural Resiniferatoxin for the Treatment of Intractable Pain Associated With Advanced Cancer

Conditions
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Pain, Intractable, Pain Cancer, Pain

Intervention / Treatment
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* Drug: Resiniferatoxin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed advanced cancer Targeted pain area of involvement that is at or below the lower thoracic or chest level down to lower extremities, attributed to the cancer If pain is present in other areas, able to differentiate pain in the target area is the primary source of pain Intractable pain that has not responded to standard therapies Be opioid tolerant, defined as an average daily opioid consumption > 30 mg oral morphine equivalent dose during the screening and which has been stable for the month prior to screening Have a Karnofsky Performance Scale score ≥ 50 at Screening In the Investigator's opinion, a reasonable expectation that the subject will be able to complete the study Able to comply with the study procedures and give informed consent Willing to follow contraception guidelines Exclusion Criteria: Be undergoing or have plans to undergo changes to current cancer treatment from D-7 through M3 Had an implantation of intrathecal pump or spinal cord stimulator less than 6 weeks prior to D1 or planning to undergo such a placement during the study prior to M3 Have leptomeningeal metastases in the lumbar area Unless approachable via the caudal route, have the level of intended epidural injection within site of prior lumbar spine surgical procedures that could disrupt the epidural space or otherwise impair ability of the injection to reach nerves Has evidence of a non-correctable coagulopathy or hemostasis problem including a low platelet count, prothrombin time, abnormal PT or PTT, or on anticoagulant or antiplatelet therapies before and during investigational product (IP) administration Have evidence or history of bleeding disorder or disseminated intravascular coagulation, any recent hemorrhage or bleeding event within 4 weeks prior to D1 Have abnormal neutrophil or serum creatinine Is febrile or has other evidence of infection within 24 hours of D1 Has recently been diagnosed as COVID-19 positive or evidence of active infection. The subject may participate if full recovery has occurred with a negative RT-PCR test (any EUA cleared test) at least 1 week prior to D1 Has an allergy or hypersensitivity to TRPV1 agonists, bupivacaine, radiographic contrast agents, fentanyl, hydromorphone, or morphine Pregnant at Screening or planning on becoming pregnant or currently breastfeeding Has an intrathecal shunt, increased intracranial pressure or evidence of brain pathology as determined by symptoms, history, physical examination, and/or magnetic resonance imaging (MRI) Is unable or distinguish the target pain from any additional loci of pain at screening Non-study related minor surgical procedure ≤ 2 days or major surgical procedure ≤ 7 days prior to screening and must be sufficiently recovered and stable prior to D1 Has not recovered from toxicities from previous cancer treatment, including chemotherapy, hormone therapy, immunotherapy, radiotherapy or bisphosphonates. Participants are not eligible if they have received such therapy within the month prior to D1 Non-study related minor surgical procedure ≤ 5 days or major surgical procedure ≤ 21 days prior to enrollment. In all cases, subjects must be sufficiently recovered and stable prior to IP administration on D1 Arterial thrombi, myocardial infarction, admission for unstable angina, within 3 months prior to screening Clinically significant electrocardiogram abnormalities Have any medical condition that could adversely impact subject's participation or safety or interfere with pain assessments Participation in another investigational trial during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Resiniferatoxin<br>15 mcg, 20 mcg, or 25 mcg in 2mL injected once into the epidural space | Drug: Resiniferatoxin<br>* Resiniferatoxin is a compound purified from natural sources<br>* Other names: RTX;|
| Placebo Comparator: Placebo<br>2mL injected once into the epidural space | Drug: Placebo<br>* Vehicle solution<br>|
| No Intervention: Concurrent Control<br>No intervention | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the incidence of any treatment-emergent adverse events of epidural Resiniferatoxin (RTX) [safety and tolerability] | To assess the safety of epidural RTX including incidence and severity of any short-term and long-term treatment-emergent adverse events (TEAEs) using the Common Terminology Criteria for Adverse Events (CTCAE) criteria | Baseline through study completion at up to approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess efficacy of RTX on pain associated with advanced cancer | To assess efficacy of each epidural RTX dose in comparison to control groups on the subject's intractable pain due to advanced cancer using the Brief Pain Inventory, Short Form (BPI-SF) score (1-10, with 10 associated with worse pain) | Baseline through study completion at up to approximately 12 months | 
| Assess RTX effect on quality of life | To assess the efficacy of each epidural RTX dose in comparison to control groups on the quality of life using Treatment Helpfulness Questionnaire score (graded 1-7, with 7 being most helpful) | Baseline through study completion at up to approximately 12 months | 
| Assess RTX effect on opioid consumption | To assess the effect of each epidural RTX dose on opioid consumption, measuring the average reduction compared to baseline of daily opioid consumption, calculated as an oral morphine equivalent dose | Baseline through study completion at up to approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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advanced cancer pain, cancer pain, pain, resiniferatoxin, RTX