Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

NCT00804154 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 09003909-N-0039
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Intractable Pain; Palliative Care

Keywords

Vanilloid; Capsaicin; Cancer Pain; Nerve Block

Outcome Measures

Primary Outcomes (1)

• 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 es...

  Dose escalation decisions are based on both effectiveness (as assessed by mean worst pain on the NRS) and DLT. The dose escalation population will include all subjects who are dosed, complete the NRS, and have the DLT assessments from baseline through Day 15. Subjects who are not evaluable for dose escalation will be replaced.

  Day 7, Day 15, Day 68, Day 188

Secondary Outcomes (1)

• Secondary outcome measures will be other surveys of pain, including an assessment of worst daily pain by the visual analog scale, and assessments of function and quality of life.

  Day 7, Day 15, Day 68, Day 188

Study Arms (1)

Single Arm

EXPERIMENTAL

advanced cancer patients with pain

Drug: Intrathecal Resiniferatoxin

Interventions

Intrathecal Resiniferatoxin DRUG

phase I, single-site, non-randomized, open-label, dose-escalation study to determine the safety and efficacy of IT RTX in subjects with severe refractory pain due to advanced malignancy

Single Arm

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older.
• Clinical and histological diagnosis of cancer with disease that has not adequately responded to standard therapies. A pathology report documenting malignancy is required.
• 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.
• Alternative methods of pain control are not sufficiently effective, not indicated, not tolerated, and/or refused by the subject, as determined by the Pain and Palliative Care Service (PPCS). Alternative methods of pain control include, but are not limited to, the following:
• Opioids (all routes of administration including neuraxial infusions)
• Adjuvant pain medications such as antidepressants, corticosteroids, local anesthetics, and antiseizure medications
• Procedures such as catheter or implantable pump placement for delivery of analgesic medication
• Prior neurolytic interventions (including intercostal, superior hypogastric, or celiac plexus blocks)
• Complementary medicine approaches
• Transcutaneous electric nerve stimulation
• Radiation therapy
• Reasonable expectation that the subject will be able to complete the study through the 30-day follow-up.
• Medical clearance from referring physician consisting of a statement indicating an adequate recovery period from other previous trials/medication.
• the study by 3 separate persons:
• Principal Investigator (PI) or an Associate Investigator (AI)

You may not qualify if:

• Subjects will be excluded from the study if they meet any of the following criteria:
• Primary pain source from anatomical regions at T5 dermatome or above.
• Pain due to causes other than cancer or its treatment that is moderate to severe in intensity.
• Anatomic abnormality or pathology of the spinal cord and/or IT space on magnetic resonance imaging (MRI) that could increase the risk of adverse effects of catheter placement or interfere with CSF flow.
• Evidence of advanced brain pathology or elevated intracranial pressure as determined by symptoms, history, physical examination (including neurological and eye examination), and/or MRI.
• Presence of an IT shunt device (e.g., ventriculo-peritoneal and ventriculo-atrial shunts).
• Anticipating initiation of palliative anti-tumor therapy or significant changes to current palliative anti-tumor therapy before completion of the Day 15 visit.
• Documented allergy to chili peppers or capsaicin (e.g., hives, wheal).
• Contraindication to MRI or MRI contrast.
• Female subjects who are pregnant or lactating.
• Clinically significant disorder or condition that might interfere with study participation or greatly increase safety risk to the subject, as judged by a study investigator.
• Planned use of another investigational agent, therapy, or device within 30 days after dosing.
• Have a history of heart failure or unexplained fainting (syncope).
• Have an EKG abnormality in which the baseline QTc interval exceeds 450 milliseconds.
• Have a known family history of long QT syndrome.

Sponsors & Collaborators

• Sorrento Therapeutics, Inc.: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Dental and Craniofacial Research (NIDCR): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (4)

• Daut RL, Cleeland CS. The prevalence and severity of pain in cancer. Cancer. 1982 Nov 1;50(9):1913-8. doi: 10.1002/1097-0142(19821101)50:93.0.co;2-r.

  PMID: 7116316 BACKGROUND

• Cleeland CS, Gonin R, Hatfield AK, Edmonson JH, Blum RH, Stewart JA, Pandya KJ. Pain and its treatment in outpatients with metastatic cancer. N Engl J Med. 1994 Mar 3;330(9):592-6. doi: 10.1056/NEJM199403033300902.

  PMID: 7508092 BACKGROUND

• Oster MW, Vizel M, Turgeon LR. Pain of terminal cancer patients. Arch Intern Med. 1978 Dec;138(12):1801-2.

  PMID: 718345 BACKGROUND

• Mannes AJ, Heiss JD, Berger A, Alewine CC, Butman JA, Hughes MS, Rabbee N, Hayes C, Williams TS, Sapio MR, Iadarola MJ. Treatment of Intractable Cancer Pain with Resiniferatoxin - An Interim Study. NEJM Evid. 2025 Jun;4(6):EVIDoa2400423. doi: 10.1056/EVIDoa2400423. Epub 2025 May 27.

  PMID: 40423401 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Pain, Intractable; Cancer Pain

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

John D Heiss, M.D.

CONTACT

Not Listed; SNBrecruiting@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: December 5, 2008
• First Posted: December 8, 2008
• Study Start: August 14, 2009
• Primary Completion (Estimated): February 7, 2027
• Study Completion (Estimated): February 7, 2027
• Last Updated: June 8, 2026

Record last verified: 2025-12-16

Locations

US (1)