Resiniferatoxin for Chronic Pain in Advanced Cancer

Recruiting at 1 trial location

Overseen By John D Heiss, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Must not be taking: Anticoagulants, Antiplatelets

Disqualifiers: Brain pathology, Pregnancy, Heart failure, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 11

Duration: 2 days

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of an experimental drug called resiniferatoxin (RTX) for treating severe pain in people with advanced cancer. RTX, derived from a cactus-like plant, destroys nerves that send pain signals. The trial seeks participants with advanced cancer who experience severe pain in the chest or below that isn't controlled by other treatments. Participants will receive an RTX injection and undergo close monitoring to assess the drug's effects on their pain and overall health. As a Phase 1 trial, this research aims to understand how RTX works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you must be able to stop any blood thinners (like aspirin) before and during the procedure. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that resiniferatoxin is likely to be safe for humans?

In earlier studies, resiniferatoxin (RTX) has shown potential in helping people with advanced cancer manage severe pain. Research suggests that RTX can reduce pain without the need for opioids, which are strong painkillers with many side effects. RTX targets and destroys certain nerves that send pain signals.

Regarding safety, RTX remains under close study. Reports from past research indicate that it is generally well-tolerated. However, since RTX is in early testing stages, unknown risks may still exist. Participants experienced some side effects, mostly mild and temporary, though specific details were not provided in the available data.

Anyone considering joining a trial should know that current information is based on early studies. While some safety information exists, more research is needed to fully understand the risks. Participants will be carefully monitored throughout the trial to ensure their safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Resiniferatoxin is unique because it targets chronic pain in advanced cancer patients by acting on the nerve cells responsible for pain sensation. Unlike standard pain treatments, like opioids which work by dulling the pain sensation throughout the body, resiniferatoxin specifically binds to and desensitizes the TRPV1 receptor on pain-conducting nerves, potentially reducing pain without the systemic side effects often associated with traditional pain relief methods. Researchers are excited about this treatment because it could offer more targeted pain relief with fewer side effects, improving the quality of life for patients with advanced cancer.

What evidence suggests that resiniferatoxin might be an effective treatment for chronic pain in advanced cancer?

Research has shown that resiniferatoxin (RTX) can effectively reduce severe pain in patients with advanced cancer. One study found that a single injection of RTX provided long-lasting pain relief and reduced the need for opioids, which are strong painkillers. RTX works by destroying the nerves that send pain signals to the brain, similar to the action of the spicy compound in hot peppers. In animal studies, RTX successfully relieved pain and decreased the need for additional pain medications. These findings suggest that RTX could be a promising option for managing severe cancer pain. Participants in this trial will receive RTX to evaluate its effectiveness in reducing chronic pain in advanced cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

John D Heiss, M.D.

Principal Investigator

National Institute of Neurological Disorders and Stroke (NINDS)

Are You a Good Fit for This Trial?

Adults over 18 with severe pain from advanced cancer below the chest level, uncontrolled by standard treatments. Participants must not be on curative cancer therapy but can continue established palliative care. They should have a high daily pain score, be able to complete follow-ups for 30 days, and agree to use contraception if applicable. Exclusions include those with certain medical conditions or devices, pregnant women, and those allergic to chili peppers or capsaicin.

Inclusion Criteria

Standard pain treatments haven't worked for me, as confirmed by a pain specialist.

Other pain treatments haven't worked for me or I've refused them.

My worst daily pain level is 6 or more, related to cancer below my chest.

Exclusion Criteria

My main pain source is above my mid-chest area.

You have a spinal cord or intrathecal space issue that could make it risky to place a catheter or affect the flow of cerebrospinal fluid.

I have advanced brain issues or high pressure in my brain, confirmed by tests or symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pretreatment Visit

Participants undergo medical history review, physical examination, and various tests including EKG, blood draw, urinalysis, neurological exams, and MRI

1 day

1 visit (in-person)

Treatment

RTX is injected intrathecally under general anesthesia, followed by monitoring and sample collection

2 days

2-day hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up visits and phone calls

6 months

Visits on days 7, 14, 30, and monthly follow-up calls

What Are the Treatments Tested in This Trial?

Interventions

• Resiniferatoxin

Trial Overview The trial tests Resiniferatoxin (RTX), an experimental drug derived from a plant similar to hot pepper's active ingredient. It aims at relieving severe cancer-associated pain by destroying nerves that transmit pain signals. The study involves pretreatment assessments, RTX injection under anesthesia during hospitalization with monitoring of symptoms and side effects through blood draws and MRIs followed by outpatient follow-up visits.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

advanced cancer patients with pain

Who Is Running the Clinical Trial?

National Institute of Dental and Craniofacial Research (NIDCR)

Lead Sponsor

Trials

312

Recruited

853,000+

Sorrento Therapeutics, Inc.

Industry Sponsor

Trials

48

Recruited

2,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

Published Research Related to This Trial

Epidural administration of resiniferatoxin (RTX) in rats resulted in significant and long-lasting pain relief, being 25 times more effective than subcutaneous administration, demonstrating its potential for targeted pain management.

The analgesic effect of epidural RTX was selective to the lumbar spinal region, providing profound desensitization of pain without affecting other areas, which suggests a promising approach for localized cancer pain treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epidural resiniferatoxin induced prolonged regional analgesia to pain. Szabo, T., Olah, Z., Iadarola, MJ., et al.[2019]

Resiniferatoxin effectively targets and ablates pain-generating cells in the peripheral nervous system, leading to a loss of sensitivity to heat stimuli in adult mice, while also affecting sensitivity to specific pain-related chemical stimuli.

The treatment results in a complex change in sensory perception, causing desensitization to heat and sensitization to cold, suggesting that surviving sensory neurons may compensate for lost pain signals, highlighting the intricate balance of pain and temperature sensation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. Pecze, L., Pelsoczi, P., Kecskés, M., et al.[2019]

Resiniferatoxin (RTX) is a highly potent TRPV1 agonist that offers enhanced efficacy and longer-lasting pain relief compared to traditional treatments, making it a promising option for pain management.

RTX can be administered both centrally and peripherally, allowing for targeted treatment of various pain conditions, particularly in patients with advanced cancer, and enabling a personalized approach to pain therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine. Iadarola, MJ., Gonnella, GL.[2022]

Intrathecal administration of resiniferatoxin in dogs leads to significant and prolonged pain relief from bone cancer, with comfort scores improving significantly at 2, 6, 10, and 14 weeks post-treatment.

The treatment resulted in a reduction or discontinuation of supplemental pain medications in 67% of the dogs, indicating its efficacy in managing pain while also causing transient increases in blood pressure and heart rate immediately after administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model. Brown, DC., Iadarola, MJ., Perkowski, SZ., et al.[2022]

Resiniferatoxin (RTX) is a powerful pain relief treatment that can effectively desensitize pain perception and reduce inflammation without significant side effects, making it a promising option for various pain management scenarios.

RTX has shown effectiveness in restoring bladder control in patients with detrusor overactivity and is currently being tested for treating knee pain in osteoarthritis, indicating its potential for targeted pain therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents. Szallasi, A.[2023]

Citations

1. ninds.nih.gov ninds.nih.gov/health-information/clinical-trials/resiniferatoxin-treat-severe-pain-associated-advanced-cancer

Resiniferatoxin to Treat Severe Pain Associated With ... This study will examine the safety of giving the experimental drug, resiniferatoxin (RTX), to treat severe pain in patients with advanced cancer.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00804154

NCT00804154 | Resiniferatoxin to Treat Severe Pain ... This study will examine the safety of giving the experimental drug, resiniferatoxin (RTX), to treat severe pain in patients with advanced cancer.

3. evidence.nejm.org evidence.nejm.org/doi/abs/10.1056/EVIDoa2400423

Treatment of Intractable Cancer Pain with Resiniferatoxin The primary outcome was safety. Secondary outcomes were efficacy assessed over the course of the study using a numerical rating scale measuring ...

4. nih.gov nih.gov/news-events/news-releases/nih-scientists-pioneer-promising-treatment-intractable-cancer-pain

NIH scientists pioneer promising treatment for intractable ... A single injection of RTX provided patients durable relief. Patients' need for pain-relieving opioids declined sharply, and their quality of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02522611

NCT02522611 | Periganglionic Resiniferatoxin for the ... To investigate the safety and efficacy of RTX administered intrathecally in subjects with severe refractory pain associated with advanced cancer along with ...

6. jpain.org jpain.org/article/S1526-5900(14)00303-4/fulltext

(364) A Phase I study of the intrathecal administration ... We are conducting a phase I clinical trial of intrathecal administration of resiniferatoxin (RTX) in advanced cancer patients with severe, medically-refractory ...