RECRUITING

Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer

Conditions

Intractable Pain Palliative Care Vanilloid Capsaicin Cancer Pain Nerve Block

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer

Quick Facts

Study Start:2009-08-14

Study Completion:2025-02-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT00804154

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 99 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age 18 years or older. 2. Clinical and histological diagnosis of cancer with disease that has not adequately responded to standard therapies. A pathology report documenting malignancy is required. 3. Subject not currently seeking or receiving potentially curative therapies for cancer (e.g., chemotherapy or immunotherapy). Curative cancer therapy may be sought after the Day 15 clinic visit, and palliative anti-tumor therapy is allowed as long as the subject was established on that therapy prior to enrollment (see exclusion criterion 6). 4. 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. 5. 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: * Prior neurolytic interventions (including intercostal, superior hypogastric, or celiac plexus blocks) * Complementary medicine approaches * Transcutaneous electric nerve stimulation * Radiation therapy 6. Reasonable expectation that the subject will be able to complete the study through the 30-day follow-up. 7. Medical clearance from referring physician consisting of a statement indicating an adequate recovery period from other previous trials/medication. 8. Formal review of the subject s medical records and written approval for his/her inclusion in * Principal Investigator (PI) or an Associate Investigator (AI) * Medical oncologist or oncologic surgeon. * A member of the PPCS at the NIH or institution s equivalent at other sites. 10. International normalized ratio (INR; from prothrombin time \[PT\]) \< 1.5 and partial thromboplastin time (PTT) less than or equal to the upper limit of the reference range. The INR and PTT may be corrected (e.g., by administration of blood products, vitamin K, etc.), provided a repeat blood draw confirms that the values meet this inclusion criterion. 10. Platelet count greater than or equal to 50,000/mm\^3. Platelets will be transfused as necessary to raise the platelet count to greater than or equal to 100,000/mm\^3 prior to dosing. 11. Ability to stop any anticoagulant (e.g., Coumadin) and antiplatelet therapies (e.g., aspirin) before and during IT catheter placement according to accepted medical guidelines.1 12. Ability and willingness to undergo an eye examination. 13. Ability to read, speak, and understand English, and willingness to complete the study tools and forms. 14. For women of childbearing potential and men with partners of childbearing potential, the ability and willingness to 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, or * surgical sterilization (hysterectomy, tubal ligation, or vasectomy). 15. Availability of a responsible adult to assist with activities of daily living as needed for the subject through the Day 15 visit. 16. Ability to assign a Durable Power of Attorney (DPA) for research and medical care at NIH	1. Primary pain source from anatomical regions at T5 dermatome or above. 2. Pain due to causes other than cancer or its treatment that is moderate to severe in intensity. 3. 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. 4. Evidence of advanced brain pathology or elevated intracranial pressure as determined by symptoms, history, physical examination (including neurological and eye examination), and/or MRI. 5. Presence of an IT shunt device (e.g., ventriculo-peritoneal and ventriculo-atrial shunts). 6. Anticipating initiation of palliative anti-tumor therapy or significant changes to current palliative anti-tumor therapy before completion of the Day 15 visit. 7. Documented allergy to chili peppers or capsaicin (e.g., hives, wheal). 8. Contraindication to MRI or MRI contrast. 9. Female subjects who are pregnant or lactating. 10. 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. 11. Planned use of another investigational agent, therapy, or device within 30 days after dosing. 12. Have a history of heart failure or unexplained fainting (syncope). 13. Have an EKG abnormality in which the baseline QTc interval exceeds 450 milliseconds. 14. Have a known family history of long QT syndrome. 15. Have abnormal electrolyte levels (i.e., low potassium) that cannot be corrected. 16. Have urinary retention that does not resolve with medical or surgical treatment. 17. Have skin ulceration that does not resolve with medical or surgical treatment. 18. Have a history of seizure activity in the previous month. 19. Have experienced symptoms of opioid toxicity in the past month (i.e. myoclonus, seizures, and/or hallucinations)

Inclusion Criteria

Exclusion Criteria

1. Age 18 years or older.
2. Clinical and histological diagnosis of cancer with disease that has not adequately responded to standard therapies. A pathology report documenting malignancy is required.
3. Subject not currently seeking or receiving potentially curative therapies for cancer (e.g., chemotherapy or immunotherapy). Curative cancer therapy may be sought after the Day 15 clinic visit, and palliative anti-tumor therapy is allowed as long as the subject was established on that therapy prior to enrollment (see exclusion criterion 6).
4. 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.
5. 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:
* Prior neurolytic interventions (including intercostal, superior hypogastric, or celiac plexus blocks)
* Complementary medicine approaches
* Transcutaneous electric nerve stimulation
* Radiation therapy
6. Reasonable expectation that the subject will be able to complete the study through the 30-day follow-up.
7. Medical clearance from referring physician consisting of a statement indicating an adequate recovery period from other previous trials/medication.
8. Formal review of the subject s medical records and written approval for his/her inclusion in
* Principal Investigator (PI) or an Associate Investigator (AI)
* Medical oncologist or oncologic surgeon.
* A member of the PPCS at the NIH or institution s equivalent at other sites.
10. International normalized ratio (INR; from prothrombin time \[PT\]) \< 1.5 and partial thromboplastin time (PTT) less than or equal to the upper limit of the reference range. The INR and PTT may be corrected (e.g., by administration of blood products, vitamin K, etc.), provided a repeat blood draw confirms that the values meet this inclusion criterion.
10. Platelet count greater than or equal to 50,000/mm\^3. Platelets will be transfused as necessary to raise the platelet count to greater than or equal to 100,000/mm\^3 prior to dosing.
11. Ability to stop any anticoagulant (e.g., Coumadin) and antiplatelet therapies (e.g., aspirin) before and during IT catheter placement according to accepted medical guidelines.1
12. Ability and willingness to undergo an eye examination.
13. Ability to read, speak, and understand English, and willingness to complete the study tools and forms.
14. For women of childbearing potential and men with partners of childbearing potential, the ability and willingness to 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, or
* surgical sterilization (hysterectomy, tubal ligation, or vasectomy).
15. Availability of a responsible adult to assist with activities of daily living as needed for the subject through the Day 15 visit.
16. Ability to assign a Durable Power of Attorney (DPA) for research and medical care at NIH

1. Primary pain source from anatomical regions at T5 dermatome or above.
2. Pain due to causes other than cancer or its treatment that is moderate to severe in intensity.
3. 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.
4. Evidence of advanced brain pathology or elevated intracranial pressure as determined by symptoms, history, physical examination (including neurological and eye examination), and/or MRI.
5. Presence of an IT shunt device (e.g., ventriculo-peritoneal and ventriculo-atrial shunts).
6. Anticipating initiation of palliative anti-tumor therapy or significant changes to current palliative anti-tumor therapy before completion of the Day 15 visit.
7. Documented allergy to chili peppers or capsaicin (e.g., hives, wheal).
8. Contraindication to MRI or MRI contrast.
9. Female subjects who are pregnant or lactating.
10. 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.
11. Planned use of another investigational agent, therapy, or device within 30 days after dosing.
12. Have a history of heart failure or unexplained fainting (syncope).
13. Have an EKG abnormality in which the baseline QTc interval exceeds 450 milliseconds.
14. Have a known family history of long QT syndrome.
15. Have abnormal electrolyte levels (i.e., low potassium) that cannot be corrected.
16. Have urinary retention that does not resolve with medical or surgical treatment.
17. Have skin ulceration that does not resolve with medical or surgical treatment.
18. Have a history of seizure activity in the previous month.
19. Have experienced symptoms of opioid toxicity in the past month (i.e. myoclonus, seizures, and/or hallucinations)

Contacts and Locations

Study Contact

John D Heiss, M.D.

CONTACT

Not Listed

SNBrecruiting@nih.gov

Principal Investigator

John D Heiss, M.D.

PRINCIPAL_INVESTIGATOR

National Institute of Neurological Disorders and Stroke (NINDS)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

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

John D Heiss, M.D., PRINCIPAL_INVESTIGATOR, National Institute of Neurological Disorders and Stroke (NINDS)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2009-08-14

Study Completion Date2025-02-07

Study Record Updates

Study Start Date2009-08-14

Study Completion Date2025-02-07

Terms related to this study

Keywords Provided by Researchers

Vanilloid
Capsaicin
Cancer Pain
Nerve Block

Additional Relevant MeSH Terms

Intractable Pain
Palliative Care