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 study will examine the safety of giving the experimental drug, resiniferatoxin (RTX), to treat severe pain in patients with advanced cancer. RTX is a chemical extracted from a cactus-like plant. It is similar to capsaicin, the active ingredient in hot pepper. RTX has relieved pain and reduced the need for pain medication in several animal experiments. It works by destroying nerves that transmit pain information. People at least 18 years of age with severe pain from advanced cancer at or below the level of the chest that cannot be controlled with standard treatments may be eligible for this study. Participants undergo the following procedures: Pretreatment Visit Before beginning treatment with RTX, patients give a medical history and undergo a physical examination that includes: * Electrocardiogram (EKG) * Blood draw * Urinalysis * Neurological examinations * Peak expiratory flow rate (PEFR) * Eye examination * MRI * Urology assessment * Pregnancy test, when appropriate * Questionnaires to collect information on health, personality, mood, pain levels and symptoms. 2-Day Hospitalization Patients are hospitalized for 2 days for RTX injection and monitoring, as follows: * RTX injection: RTX is injected in the operating room under general anesthesia. It is given through a catheter placed in the patient s spine. The catheter is also used to obtain samples of cerebrospinal fluid (CSF) the clear fluid that bathes the spinal cord. The fluid is examined to assess drug effects and side effects, chemical changes in the content of the CSF associated with RTX, and how RTX is handled by the body. * Post-injection monitoring, including: * Surveys about symptoms such as pain or weakness * Neurological examinations * Blood and CSF sampling * EKG * AEs Outpatient followup * Vitals * Blood draw, Urinalysis, neurological and sensory testing, EKG on days 7, 14 and 30 after the injection * MRI scans of the head and back, Urology assessment and PEFR on day 15 after the injection * Eye examination * Follow-up phone calls monthly for 6 months

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.

How is the drug resiniferatoxin (RTX) unique in treating chronic pain in advanced cancer?

Resiniferatoxin (RTX) is unique because it is an ultrapotent analog of capsaicin that targets specific nerve cells responsible for pain, providing long-lasting pain relief with minimal side effects. It can be administered directly to the spinal cord or affected area, allowing for precise and effective pain management tailored to individual needs. ^{1 2 3 4 5}

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

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]

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]

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]

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 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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. Netherlands pubmed.ncbi.nlm.nih.gov

Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Epidural resiniferatoxin induced prolonged regional analgesia to pain. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. [2019]