Resiniferatoxin for Chronic Pain in Advanced Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by John D Heiss, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

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}

Eligibility Criteria

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.

I am 18 years old or older.

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Resiniferatoxin (Neurotoxin)

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.

Participant Groups

Group I: Single Arm Experimental Treatment 1 Intervention

advanced cancer patients with pain

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

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

Sorrento Therapeutics, Inc. Industry Sponsor

National Institute of Neurological Disorders and Stroke (NINDS) Collaborator

References

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

Resiniferatoxin: Nature's Precision Medicine to Silence TRPV1-Positive Afferents. [2023] Resiniferatoxin (RTX) is an ultrapotent capsaicin analog with a unique spectrum of pharmacological actions. The therapeutic window of RTX is broad, allowing for the full desensitization of pain perception and neurogenic inflammation without causing unacceptable side effects. Intravesical RTX was shown to restore continence in a subset of patients with idiopathic and neurogenic detrusor overactivity. RTX can also ablate sensory neurons as a "molecular scalpel" to achieve permanent analgesia. This targeted (intrathecal or epidural) RTX therapy holds great promise in cancer pain management. Intra-articular RTX is undergoing clinical trials to treat moderate-to-severe knee pain in patients with osteoarthritis. Similar targeted approaches may be useful in the management of post-operative pain or pain associated with severe burn injuries. The current state of this field is reviewed, from preclinical studies through veterinary medicine to clinical trials.

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

Resiniferatoxin for Pain Treatment: An Interventional Approach to Personalized Pain Medicine. [2022] This review examines existing preclinical and clinical studies related to resiniferatoxin (RTX) and its potential uses in pain treatment. Like capsaicin, RTX is a vanilloid receptor (TRPV1) agonist, only more potent. This increased potency confers both quantitative and qualitative advantages in terms of drug action on the TRPV1 containing nerve terminal, which result in an increased efficacy and a long duration of action. RTX can be delivered by a central route of administration through injection into the subarachnoid space around the lumbosacral spinal cord. It can also be administered peripherally into a region of skin or deep tissue where primary afferents nerves terminate, or directly into a nerve trunk or a dorsal root ganglion. The central route is currently being evaluated as a treatment for intractable pain in patients with advanced cancer. Peripheral administration offers the possibility to treat a wide diversity of pain problems because of the ability to bring the treatment to the site of the pain (the peripheral generator). While not all pain disorders are appropriate for RTX, tailoring treatment to an individual patient's needs via a selective and local intervention that chemically targets a specific population of nerve terminals provides a new capability for pain therapy and a simplified and effective approach to personalized pain medicine.

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

Epidural resiniferatoxin induced prolonged regional analgesia to pain. [2019] Adequate treatment of cancer pain remains a significant clinical problem. To reduce side effects of treatment, intrathecal and epidural routes of administration have been used where appropriate to reduce the total dose of agent administered while achieving regional control. Resiniferatoxin (RTX), an ultrapotent capsaicin analog, gives long-term desensitization of nociception via C-fiber sensory neurons. We evaluate here the analgesic effect on rats of epidurally administered RTX, using latency of response to a thermal stimulus in unrestrained animals. Results were compared with those for systemically administered RTX. Vehicle or graded doses of RTX were injected subcutaneously (s.c.) or through an indwelling lumbar (L4) epidural catheter as a single dose. Both routes of application of RTX produced profound thermal analgesia, reaching a plateau within 4-6 h and showing no restoration of pain sensitivity over 7 days. Vehicle was without effect. For the epidural route, the effect was selective as expected for the targeted spinal cord region, whereas the subcutaneous administration of RTX had a generalized analgesic effect. At doses yielding a tripling of back paw withdrawal latency, epidural treatment was 25-fold more effective than the subcutaneous route of application. Consistent with the regional selectivity of the lumbar epidural route, the front paws showed no more effect than by systemic RTX treatment. Binding experiments with [3H]RTX provided further evidence of the segmental desensitization induced by epidural RTX. We conclude that epidural administration of RTX at the lumbar spinal level produces profound, long-lasting, segmental analgesia to C-fiber mediated pain in the rat.

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

Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model. [2022] Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs.

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

Resiniferatoxin mediated ablation of TRPV1+ neurons removes TRPA1 as well. [2019] Resiniferatoxin, the most potent agonist of inflammatory pain/vanilloid receptor/cation channel (TRPV1) can be used for neuron subtype specific ablation of pain generating cells at the level of the peripheral nervous system by Ca(2+)-excytotoxicity. Molecular neurosurgery is an emerging technology either to alleviate severe pain in cancer or treat/prevent different local neuropathies. Our aim was determining sensory modalities that may be lost after resiniferatoxin treatment.