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Protocol Details

A Multicenter, Open-Label, Phase 1b Study to Assess the Safety and Define the Maximally Tolerated Dose of Epidural Resiniferatoxin Injection for the Treatment of Intractable Pain Associated with Cancer

This study is currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

19-N-0068

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled
Gender: Male & Female
Min Age: 18
Max Age: 100

Referral Letter Required

No

Population Exclusion(s)

Children

Special Instructions

Currently Not Provided

Keywords

Palliative Care;
Cancer Pain;
Nerve Block

Recruitment Keyword(s)

None

Condition(s)

Neoplasm Metastasis;
Questionnaires and Surveys;
Intractable Pain

Investigational Drug(s)

Resiniferatoxin

Investigational Device(s)

None

Intervention(s)

Other: Resiniferatoxin

Supporting Site

National Institute of Neurological Disorders and Stroke

Background:

Resiniferatoxin (RTX) is a drug that relieves pain by permanently destroying the nerves that send pain signals to the brain. But it may have serious side effects. Researchers want to see if RTX can treat cancer-induced pain.

Objective:

To learn whether RTX is safe and effective in treating cancer-induced pain.

Eligibility:

People ages 18 and older with intractable or stubborn pain from cancer that is not helped with any treatments they have been using

Design:

Participants will have 8 visits.

Participants will be screened in visit 1. This includes:

Medical history

Physical exam

Neurological exam

Electrocardiogram (ECG): Small sticky pads on the participant s chest will measure heart activity.

Blood and urine tests

Participants will be given an electric log to record survey answers throughout the study.

Most screening tests will be repeated at the other visits.

Participants will be called every week for a month after visit 1 to see how they are doing.

Visit 2 (day 1) will last 10 hours.

Participants must fast starting at midnight before the visit.

Participants will get RTX. They will lie flat on a table. They will be sedated. A needle will be inserted into the spine. An x-ray will make sure the needle ends up in the epidural space. The RTX will be injected into this space. Participants will then have multiple blood tests and ECGs. Visits 3-7 will take place on days 2 or 3, 8, 15, 30, and 60.

Visit 8 is the last study visit. It will take place on day 90.

Sponsoring Institution: National Institute of Neurological Disorders and Stroke

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Eligibility

INCLUSION CRITERIA:

Subjects will meet all the following inclusion criteria:

1. Histologically confirmed clinical diagnosis of advanced cancer or metastasis which has not responded to standard therapy producing intractable chronic pain in the target area (lower thoracic or chest level down to lower extremities) at Screening (V1). Intractable pain is defined as pain for which a cause cannot be removed and, according to generally accepted medical practice, the full range of pain management modalities appropriate for this subject have been used without adequate result or with intolerable side effects. This refers to subjects with pain and inadequate response to standard therapy for the pain due to cancer, as assessed by the investigator. Standard therapy typically includes, at a minimum, non-steroidal anti-inflammatory drugs (NSAIDs) and opioid-containing agents, and, in addition, other treatments and modalities considered standard of care by the investigator for the treatment of cancer pain.

2. Male or female subjects must be at least 18 years of age or older at Screening (V1).

3. Must have moderate-to-severe pain, and a worst pain score greater than or equal to 6 on the NPRS on V1

a. Subjects with multiple sites of pain are eligible as long as the pain score of the intended target pain for treatment fulfills the score of greater than or equal to 6

4. Subjects not currently seeking or receiving potentially curative therapies for cancer. Palliative therapy is acceptable if the therapy started and is stable prior to IP administration.

5. Sexually active female subjects of childbearing potential must be willing to use an effective method of contraceptive method to avoid pregnancies during the study. Male subjects capable of fathering a child must be willing to use barrier methods to avoid a pregnancy during the study.

Acceptable methods of contraception for this study include:

a. Documented tubal sterilization (tubal ligation or transcervical tubal occlusion with documentation of occlusion 6 months post-procedure) or orchiectomy

b. Intrauterine Device (IUD)

c. Two barrier methods used together (cervical/vault cap, diaphragm, or vaginal spermicide plus a male or female condom)

d. Absolute sexual abstinence (no sexual intercourse or genital contact with a male partner)

Note: The IUD can be relied upon without a second method, because pregnancy rates are as low as or lower than those achieved with 2 barrier methods. Male condoms with or without a spermicide coating should be acceptable, as some women are allergic to spermicide.

6. Must be willing and capable of understanding and cooperating with the requirements of the study including the ability to perform/undergo all required assessments for the duration of the study.

7. Must be able to read, write, understand, and complete English or Spanish study related forms and adequately communicate with the study staff in English or Spanish (using a Spanish translator).

8. Must have provided written informed consent which includes signing the institutional review board-approved consent form prior to participating in any study-related activity.

9. Subject has the reasonable expectation they will be able to complete the study (through D90 visit).

EXCLUSION CRITERIA:

The subject must not meet any of the following exclusion criteria:

1. Subjects with leptomeningeal metastases in the lumbar area.

2. Undergoing or have plans to undergo changes to current cancer treatment during the study through the D15 assessment time-point after the RTX injection. If the additional new anti-cancer treatment begins after the completion of Day 15 assessments, it is requested that the subject agree to continued participation in this trial and allow collection of follow-up data for this trial beyond Day 15 while receiving additional cancer treatments.

3. Had prior lumbar spine surgical procedures, such as posterior spinal fusions that could impair the ability to perform the injection, as assessed by the Investigator.

4. Evidence of brain pathology or increased intracranial pressure as determined by symptoms, history, physical examination, and/or magnetic resonance imaging (MRI).

5. Presence of an IT shunt.

6. Has evidence or a coagulopathy or hemostasis problem at Screening (V1) or Baseline (V2) as evidenced by:

-Prothrombin Time/International Normalized Ratio >1.3 times upper limit of normal (ULN) range with blood drawn within 1 week of the planned injection.

-Partial thromboplastin time > 1.3 times upper limit of normal (ULN) with blood drawn within 1 week of the planned injection.

-Platelet count <100,000 cells/mm3 with blood drawn within 1 week of the planned injection. upper limit of normal (UNL) with blood drawn within 1 week of the planned injection.

-Platelet count <100,000 cells/mm3 with blood drawn within 1 week of the planned injection.

Subjects must stop any anticoagulant (e.g., warfarin) or antiplatelet (e.g., aspirin) before and during IP administration according to acceptable medical guidelines. For patients on anticoagulation or antiplatelet medications not mentioned here or agents not known to affect prothrombin time (PT) or partial thromboplastin time (PTT), please contact the medical monitor. Subjects taking non-steroidal anti-inflammatory medications, or vitamin supplements that include vitamin E will be counseled either to stop taking these at least 7 days before surgery or be given instructions on dosing changes, if applicable. This requirement is standard clinical practice when undergoing elective surgical procedures to avoid surgical and postsurgical bleeding complications. Subjects with abnormal PT or PTT at Screening, but whose PT or PTT is expected to normalize once anticoagulation is held, are eligible as long as the PT or PTT has normalized prior to the planned injection. Subjects with abnormal PT or PTT, but without coagulopathy or hemostasis problems, based on an assessment by a hematology or coagulation specialist, are eligible.

7. Subjects with a total neutrophil count <1500 cells/mm3 at Screening (V1) or Baseline (V2).

8. Subjects with serum creatinine greater than or equal to 1.5 mg/dL.

9. Is febrile or has other evidence of an infection within 7 days of the planned injection.

10. Has an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic contrast agents used in diagnostic imaging studies.

11. Female subjects who are pregnant at Screening (V1) or Baseline (V2), are planning on becoming pregnant, or are currently breastfeeding.

12. Subjects with any medical condition that, in the Investigator s opinion, could impact study participation or safety, the conduct of the study, or interfere with the pain assessments.

13. Subjects who:

-have received new anti-cancer treatments (including investigational drug(s) in clinical trials) and there is less than one week or four half-lives of the investigational drug, whichever is greater, between the last dose of the new drug and the planned day of IP injection, or

-had a change in the dose or schedule of the anticancer treatments within one week or four half-lives, whichever is greater, between the last dose of the anti-cancer treatment and the planned day of IP administration, or

-are scheduled to receive a new anticancer therapy or IP (therapy or device) prior to completion of the Day 15 study visit. After Day 15 assessments, subjects may receive new therapy including investigational agents in another clinical trial while participating

in this trial. If participating in another trial, it is requested that the subject agree to continue concurrent participation in this trial including collection of follow-up data for this trial.

14. Subjects with additional loci of pain above the mid-thoracic level or other pain disorder due to non-cancer etiology at Screening (V1), unless both the investigator and the subject are clearly able to distinguish the pain due to non-cancer etiology from the target pain due to cancer. Pain from loci other than cancer is at moderate or severe intensity.

15. Liver cirrhosis or severe hepatic impairment, as assessed by the Investigator, with liver function tests (any one of AST, ALT, alkaline phosphatase, or bilirubin) three times above ULN or higher.

16. Sensory peripheral neuropathy of National Cancer Institute - CTCAE Grade 2 or higher at Screening (V1).

17. Nonstudy related minor surgical procedure less than or equal to 5 days or major surgical procedure less than or equal to 21 days prior to enrollment; in all cases, the subject must be sufficiently recovered and stable prior to IP administration on D1.

18. Subjects who have not recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies that are Grade 3 or higher by CTCAE. Subjects are eligible if the toxicities are Grade 2 or less, as long as all other inclusion/exclusion criteria are fulfilled.

19. Arterial thrombi (including stroke), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within the last 3 months prior to Screening (V1). Subjects on anticoagulation for DVT prophylaxis are eligible if the ASRA guidelines on regional anesthesia in subjects receiving antithrombotic or thrombolytic therapy are followed for withholding of anticoagulants and antiplatelet agents prior to D1.

20. Corrected QT using Fridericia s formula (QTcF) prolongation defined as a QTcF interval greater than or equal to 480 msec, clinically significant arrhythmias, or clinically significant ECG abnormalities.

21. Evidence or history of bleeding disorder, i.e., any hemorrhage or bleeding event of CTCAE >Grade 1 within 4 weeks prior to IP administration on D1.

22. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C. Known positive tests for HIV-1 or -2 antibodies, hepatitis B surface antigen, or hepatitis C antibodies. Subjects who have had chronic hepatitis B or hepatitis C infections are eligible as long as the subjects have previously received anti-viral therapy, have a viral load measured within 30 days of screening of zero, and do not fall under exclusions 6 and 15.


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Citations:

Not Provided

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Contacts:

Principal Investigator

Referral Contact

For more information:

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



John D. Heiss, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 10 RM 3D20
10 CENTER DR
BETHESDA MD 20814
(301) 594-8112
heissj@ninds.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

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