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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02522611
Recruitment Status : Not yet recruiting
First Posted : August 13, 2015
Last Update Posted : August 6, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) )

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.

...


Condition or disease Intervention/treatment Phase
Intractable Pain Palliative Care Drug: Resiniferatoxin Phase 1 Phase 2

Show Show detailed description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1b Safety and Efficacy Trial of Periganglionic Resiniferatoxin for the Treatment of Intractable Pain Due to Cancer-Induced Bone Pain
Study Start Date : August 12, 2015
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 31, 2022

Arm Intervention/treatment
Experimental: Resiniferatoxin
Schedule a maximum of 3 periganglionic DRG injection(s) at contiguous level(s) to treat targetedDRG responsible for chronic CIBP
Drug: Resiniferatoxin
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.




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) [ Time Frame: Completion of study ]
    MTD will be defined as 1 dose level below that at which dose-limiting toxicity (DLT) is observed in more than one third of the subjects.

  2. Safety/toxicity profile [ Time Frame: Completion of study ]
    The Investigator will assess the AE for severity and relationship of the AE to RTX or the injection (causality determination of the AE toeither the RTX or the injection procedure itself).

  3. Identify dose-limiting toxicities (DLT) [ Time Frame: Completion of study ]
    DLT is defined as the development in a subject of a CTCAE grade 3 or higher agent-related toxicity or two or more grade 2 agentrelatedtoxicities occurring in the same subject at any time from dosing through the D14 visit.


Secondary Outcome Measures :
  1. Improved pain relief through the 180-day time point compared to baseline [ Time Frame: Completion of study ]
    The average of the daily worst NRS scores will be used throughout the study for post-injection visits.

  2. Substantially reduced (20%) pain at the 30-, 60-. 90-, and 180-day post-treatment time points compared to the pain experienced at baseline [ Time Frame: Completion of study ]
    The average of the daily worst NRS scores will be used throughout the study for post-injection visits.

  3. Substantially reduced (20%) concomitant opioid analgesic consumption [ Time Frame: Completion of study ]
    The average of the daily worst NRS scores will be used throughout the study for post-injection visits.

  4. Improved quality of life [ Time Frame: Completion of study ]
    The BPI is a validated tool designed to assess the severity of pain and the impact of pain on daily functions in patients with cancer pain and pain due to other chronic diseases.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 150 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

-INCLUSION CRITERIA:

  1. Male or female subjects must be at least 18 years of age or older.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Must be healthy enough to tolerate study procedures in the judgment of the investigator.
  7. 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.
  8. Formal review of the subject s medical records and written approval for his/her inclusion in the study by 3 separate persons:

    • 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.
  9. 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
    • surgical sterilization (hysterectomy, tubal ligation, or vasectomy).
  10. Medical clearance from referring physician consisting of a statement indicating an adequate recovery period from other previous trials/medication if known.
  11. Must be able and willing to undergo an eye examination.
  12. Must be able to read, speak and understand English and willing to complete the study tools and forms.
  13. Subjects must have provided written informed consent which includes signing the institutional review board (IRB)-approved consent form prior to participating in any study-related activity.
  14. Must have the capacity to provide informed consent.
  15. Must have a responsible adult to provide assistance with activities of daily living as needed for the subject through the Day 14 visit.
  16. Must have abilityAbility to assign a Durable Power of Attorney (DPA) for research and medical care at NIH.

EXCLUSION CRITERIA:

Subjects will be excluded from the study if they meet any of the following criteria:

  1. Subject must not have primary pain source from anatomical regions at T5 dermatome or above.
  2. Subject must not have pain due to causes other than cancer or its treatment that is moderate to severe in intensity.
  3. 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.
  4. 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.
  5. Subject must not have an ECG abnormality of which the baseline QTc interval exceeds one-half second (500 milliseconds).
  6. Subjects must not have an allergy or hypersensitivity to chili peppers, capsaicin or radiographic contrast agents.
  7. 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.
  8. Subject must not have a contraindication to MRI or MRI contrast..
  9. 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.
  10. 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.
  11. 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).
  12. Subjects must not have abnormal electrolyte levels (i.e. low potassium) that cannot be corrected.
  13. Subjects must not be febrile or have other evidence of an infection within 7 days of the planned periganglionic injection.
  14. Subjects must not have an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic contrast agents.
  15. Female subjects must not be pregnant or breastfeeding.
  16. Subjects with any medical condition that, in the Investigator s opinion, could adversely impact the subject s participation or safety, conduct of the study, or interfere with the pain assessment, such as poorly controlled diabetes or hypertension. Patients can be re-assessed for eligibility if these conditions can be controlled medically.
  17. Subjects may not have a history of heart failure or unexplained fainting (syncope).
  18. Subjects who participated in a clinical trial of an investigational drug or device within 30 days of screening visit or are scheduled to receive an investigational product within 14 days of RTX injection.
  19. Subjects must not have received invasive treatments, such as a neurolytic procedure, including surgical neurolysis, percutaneous regional or neuraxial continuous infusions (whether opioid or local anesthetic), peripheral neuromodulation or spinal cord stimulation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02522611


Contacts
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Contact: Tracy S Williams, R.N. (301) 448-5366 tracy.williams@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: John D Heiss, M.D. National Institute of Neurological Disorders and Stroke (NINDS)
Additional Information:
Publications:
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Responsible Party: National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier: NCT02522611    
Other Study ID Numbers: 150175
15-N-0175
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: August 6, 2020
Last Verified: March 17, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Neurological Disorders and Stroke (NINDS) ):
Palliative Care
Adults
Cancer Pain
Quality of Life
Additional relevant MeSH terms:
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Pain, Intractable
Pain
Neurologic Manifestations
Signs and Symptoms