Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-induced Bone Pain

NCT02522611 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 15017515-N-0175
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Cancer-induced bone pain (CIBP) is common in people with cancer. Bone cancer can also lead to anxiety, depression, and reduced mobility and quality of life. Researchers believe a research drug called resiniferatoxin (RTX) may be able to help. Objective: To learn whether RTX is safe and can reduce cancer induced bone pain. Eligibility: People ages 18 and older with CIBP that is not relieved by standard treatments Design: Participants will have up to 6 outpatient visits over about 7 months. These will include: Medical history Physical exam Blood and urine tests. Thermal testing: a disk placed on the skin to test ability to sense temperature in and around the area of pain Chest x-ray EKG: stickers are placed on the chest to measure heart signals ECG: measures electrical activity of the heart Participants will have 1 inpatient visit lasting 2-4 days. This will include: Catheter inserted into a vein in the arm. They are given anesthesia, sedation, and x-ray contrast. A needle is passed through the skin of the back to inject the RTX. Participants will keep a log of the pain medications they take after surgery. Participants will be called 1 week and 2, 3, and 4 months after the injection. Participants will be mailed surveys and questionnaires to complete 2, 3, and 4 months after the injection. ...

Conditions

Intractable Pain; Palliative Care

Keywords

Palliative Care; Adults; Cancer Pain; Quality of Life

Outcome Measures

Primary Outcomes (1)

• To investigate the safety and efficacy of RTX administered intrathecally in subjects with severe refractory pain associated with advanced cancer along with ED100, the MTD, or the maximum dose administered, whichever is achieved first during dose...

  The primary study outcome measures are related to safety and toxicity of the investigational agent. The primary study outcome measures are: DLT MTD of RTX

  Day 7, Day 15, Day 68, Day 188

Secondary Outcomes (4)

• Improved pain relief through the 180-day time point compared to baseline

  Completion of study

• Substantially reduced (20%) pain at the 30-, 60-. 90-, and 180-day post-treatment time points compared to the pain experienced at baseline

  Completion of study

• Substantially reduced (20%) concomitant opioid analgesic consumption

  Completion of study

• Improved quality of life

  Completion of study

Study Arms (1)

Resiniferatoxin

EXPERIMENTAL

Schedule a maximum of 3 periganglionic DRG injection(s) at contiguous level(s) to treat targeted DRG responsible for chronic CIBP

Drug: Resiniferatoxin

Interventions

Resiniferatoxin DRUG

Resiniferatoxin (RTX) is an ultrapotent agonist analog of capsaicin that targets a receptor expressed on specific dorsal root sensory ganglia (DRG) neurons and is expected to reduce pain within the targeted zone.

Resiniferatoxin

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects must be at least 18 years of age or older.
• Must be diagnosed with histologically-confirmed cancer-induced bone pain producing intractable chronic pain in the target area (mid thoracic or chest level down to lower extremities) which was poorly responsive to conservative therapies based on patient report, such as analgesic medication management with potent opioids with or without prior radiotherapy, bisphosphonates, or radioisotope therapy. Additionally, pain that is non-responsive to non-opioid drugs in situations where opioids were not tolerated. Conservative therapies do not include invasive treatments, such as neurolytic procedure, including surgical neurolysis, percutaneous regional or neuraxial continuous infusions (whether opioid or local anesthetic), and peripheral neuromodulation or spinal cord stimulation, but may include temporary diagnostic or therapeutic procedures.
• Not currently seeking or receiving potentially curative therapies for cancer (e.g., chemotherapy or immunotherapy). Curative cancer therapy may be sought after the Outpatient Follow Up visit 14 (D14). Palliative anti-tumor therapy is allowed as long as the subject was established on that therapy prior to enrollment.
• Must have moderate to severe pain that is not relieved by standard treatments. Mean daily worst pain NRS score of greater than or equal to 6 for pain at or below the T6 dermatome (level of the chest) that is associated with a malignant disease. The mean score must be derived from recordings on at least 4 of 7 consecutive days within 3 weeks preceding treatment.
• The subject must agree to undergo a diagnostic periganglionic injection(s) with a long-acting local anesthetic (e.g., bupivacaine) under fluoroscopic guidance which resulted in at least a 30% temporary pain reduction in the targeted pain region lasting for the expected duration of the local anesthetic used.
• Must be healthy enough to tolerate study procedures in the judgment of the investigator.
• Subjects taking aspirin, non-steroidal anti-inflammatory medications, or vitamin supplements that include vitamin E or any prophylactic anticoagulant (including but not limited to Coumadin, heparin, or Xarelto) will be counseled either to stop taking these at least 7 days before surgery or be given instructions on dosing changes if applicable. In addition, if patients are currently taking a Factor Xa inhibitor (such as Xarelto) a hematology consult will be obtained. Subjects must be willing to comply with this requirement, which is standard clinical practice when undergoing elective surgical procedures to avoid surgical and post-surgical bleeding complications.
• Principal Investigator (PI) or an Associate Investigator (AI).
• Medical oncologist or oncologic surgeon.
• A member of the Pain and Palliative Care Service (PPCS) at the NIH.
• For women of childbearing potential and men with partners of childbearing potential, the ability and willingness use an effective method of contraception during the study.
• Effective methods of birth control include:
• hormonal contraception (birth control pills, injected hormones, or vaginal ring).,
• intrauterine device.
• barrier methods (condom or diaphragm) combined with spermicide

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria:
• Subject must not have primary pain source from anatomical regions at T5 dermatome or above.
• Subject must not have pain due to causes other than cancer or its treatment that is moderate to severe in intensity.
• Subjects must not be undergoing or have plans to undergo any active treatment for their cancer during the study until after the day 14 assessment timepoint, after the RTX injection.
• Subject must not be anticipating initiation of palliative anti-tumor therapy or significant changes to current palliative anti-tumor therapy before completion of the Day 14 visit.
• Subject must not have an ECG abnormality of which the baseline QTc interval exceeds 450 milliseconds.
• Subjects must not have an allergy or hypersensitivity to chili peppers, capsaicin or radiographic contrast agents.
• Subject must not have an anatomic abnormality or pathology of the spinal cord and/or PG space on magnetic resonance imaging (MRI) that could increase the risk of adverse effects of placement of the needle.
• Subject must not have a contraindication to MRI or MRI contrast..
• Subjects must not have evidence of a coagulopathy or hemostasis problem as
• evidenced by the following blood laboratory values within the week prior to the planned injection:
• PT/INR (prothrombin time/International normalized ratio) \> 1.5 times upper limit of normal range (ULN).
• PTT (partial thromboplastin time) \> 35 seconds.
• Subjects must not have a platelet count \<50,000/mm3. Platelets will be transfused as necessary to raise the platelet count to greater than or equal to 100,000/mm3 prior to dosing.
• Subjects must not have a total neutrophil count (TNC) \<1500. The US Clinical Practice Guideline for lumbar puncture is a platelet count of 50,0000, which is higher risk for hemorrhage than periganglionic infection. Patients with TNC\<1500 (neutropenia) may be eligible later if their TNC level becomes greater than 1500 spontaneously or after use of medications stimulating granulocyte production, such as Neupogen (granulocyte colony stimulating factor: G-CSF).

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Mannes AJ, Brown DC, Keller J, Cordes L, Eckenhoff RG, Caudle RM, Iadarola MJ, Meng QC. Measurement of resiniferatoxin in serum samples by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Sep 5;823(2):184-8. doi: 10.1016/j.jchromb.2005.06.042.

  PMID: 16039169 BACKGROUND

• Neubert JK, Mannes AJ, Karai LJ, Jenkins AC, Zawatski L, Abu-Asab M, Iadarola MJ. Perineural resiniferatoxin selectively inhibits inflammatory hyperalgesia. Mol Pain. 2008 Jan 16;4:3. doi: 10.1186/1744-8069-4-3.

  PMID: 18199335 BACKGROUND

• Iadarola MJ, Mannes AJ. The vanilloid agonist resiniferatoxin for interventional-based pain control. Curr Top Med Chem. 2011;11(17):2171-9. doi: 10.2174/156802611796904942.

  PMID: 21671877 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pain, Intractable; Cancer Pain

Interventions

resiniferatoxin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• John D Heiss, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tracy S Williams, R.N.

CONTACT

(301) 448-5366; tracy.williams@nih.gov

John D Heiss, M.D.

CONTACT

(301) 594-8112; heissj@ninds.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2015
• First Posted: August 13, 2015
• Study Start (Estimated): June 27, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 12, 2026

Record last verified: 2025-09-09

Locations

US (1)