Resiniferatoxin to Treat Severe Pain Associated With Advanced Cancer
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-99
SponsorNational Institute of Dental and Craniofacial Research (NIDCR)
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Intrathecal Resiniferatoxin
Drugphase 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
Treatment groups
45 Participants
are divided into 1 treatment groupGroup A: Single ArmExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
Day 7, Day 15, Day 68, Day 188Secondary 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.
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.
Time frame
Day 7, Day 15, Day 68, Day 188Sponsors and contacts
Click on the lead sponsor to view all of their trials.
National Institute of Dental and Craniofacial Research (NIDCR)
Lead sponsor
National Institute of Neurological Disorders and Stroke (NINDS)
Collaborator
Sorrento Therapeutics, Inc.
Collaborator
Source ClinicalTrials.gov