Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer
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|ClinicalTrials.gov Identifier: NCT00804154|
Recruitment Status : Recruiting
First Posted : December 8, 2008
Last Update Posted : February 14, 2023
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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:
Before beginning treatment with RTX, patients give a medical history and undergo a physical examination that includes:
- Electrocardiogram (EKG)
- Blood draw
- Neurological examinations
- Peak expiratory flow rate (PEFR)
- Eye examination
- Urology assessment
- Pregnancy test, when appropriate
Questionnaires to collect information on health, personality, mood, pain levels and symptoms.
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
- 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
|Condition or disease||Intervention/treatment||Phase|
|Intractable Pain Palliative Care||Drug: Intrathecal Resiniferatoxin||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of the Intrathecal Administration of Resiniferatoxin for Treating Severe Refractory Pain Associated With Advanced Cancer|
|Actual Study Start Date :||August 14, 2009|
|Estimated Primary Completion Date :||August 31, 2023|
|Estimated Study Completion Date :||August 31, 2023|
Experimental: Single Arm
advanced cancer patients with pain
Drug: Intrathecal Resiniferatoxin
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
- 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... [ Time Frame: Day 7, Day 15, Day 68, Day 188 ]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.
- 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. [ Time Frame: Day 7, Day 15, Day 68, Day 188 ]The secondary outcome variables will be summarized over time by dose cohort as appropriate for the outcome measure. Absolute and percentage change in the NRS and VAS pain scores between the pre- and post-RTX dosing assessments (baseline period and study Days 8 through 14, respectively) will also be summarized.
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.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
Subject inclusion criteria are based on inadequate control of pain despite best efforts, including appropriate use of analgesic medications. To be enrolled in the study, subjects must meet all of the following criteria:
- 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.
- 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).
- 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.
- 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 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
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 intrathecal space on magnetic resonance imaging (MRI) that could increase the risk of adverse effects of intrathecal 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 intrathecal 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.
- Have abnormal electrolyte levels (i.e. low potassium) that connot be corrected.
- Have urinary retention that does not resolve with medical or surgical treatment.
- Have skin ulceration that does not resolve with medical or surgical treatment.
- Have a history of seizure activity in the previous month.
- Have experienced symptoms of opioid toxicity in the past month (i.e. myoclonus, seizures, and/or hallucinations).
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): NCT00804154
|Contact: John D Heiss, M.D.||Not Listed||SNBrecruiting@nih.gov|
|United States, Maryland|
|National Institutes of Health Clinical Center||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY dial 711 firstname.lastname@example.org|
|Principal Investigator:||John D Heiss, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|
|Responsible Party:||National Institute of Dental and Craniofacial Research (NIDCR)|
|Other Study ID Numbers:||
|First Posted:||December 8, 2008 Key Record Dates|
|Last Update Posted:||February 14, 2023|
|Last Verified:||February 10, 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Plan Description:||.We do plan to share IPD. we will share all IPD that results in a publication on a public repository, as required by most journals. the data will be de-identified and anonymized.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|