Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain
Study Details
Study Description
Brief Summary
The study is a multicenter, open-label Phase 1b single dose escalation safety study for adult subjects with intractable pain associated with cancer in any area below the mid-thoracic level who meet all other eligibility criteria.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
All subjects who received RTX will be included in the analyses and summaries of safety, efficacy, PD, and PK assessments.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RTX epidural injection Epidural injection of 1.5mL/min RTX under the guidance of epidurogram. |
Drug: Resiniferatoxin
single dose (0.4, 1, 2, 4, 8,15, 25 or 35 mcg), epidural injection
Other Names:
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Outcome Measures
Primary Outcome Measures
- Dose limiting toxicity (DLT) [3-month]
Grade 3 or 4 Toxicity associated with RTX administration
- Maximum tolerated dose (MTD) [3-month]
Maximum dose without a Grade 3 or 4 toxicity
Secondary Outcome Measures
- Numeric Pain Rating Scale (NPRS) [Day-28 to Day90 daily]
Daily average pain and daily worst pain on a 0-10 scale
Other Outcome Measures
- Daily analgesic consumption (DAC) log [Day-28 to Day90 daily]
Consumption of analgesics compared to baseline
- Brief Pain Inventory-Short Form (BPI-SF) [Day-28, Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90]
Quality of life compared to baseline by the total score
- Patient Global Impression of Change (PGIC) [Day2/3, Day8, Day15, Day30, Day60 and Day90]
Patient-reported rating of improvement on a 7-point scale, ranking the improvement from (1) to (7), with (1) being no change or worse to (7) being a great deal better and a considerable improvement that has made all the difference.
- Modified Numeric Pain Rating Scale (modified NPRS) [Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90]
A 11-point scale for rating average and worst pain at the location intended to be treated with RTX within 12 hours of the clinical visit, with 0 being no pain to 10 being worst pain imaginable.
- Modified Brief Pain Inventory-Short Form (modified BPI-SF) [Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90]
Quality of life affected by pain at the location intended to be treated with RTX, each question rates pain level and pain interference on a 0 to 10 scale. For pain level questions, 0 represents no pain and 10 represents pain as bad as can be imagined. For pain interference questions, 0 is "does not interfere" and 10 is "completely interferes".
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologically confirmed advanced cancer or metastasis, which has not responded to standard therapy, producing intractable chronic pain in any area below the mid-thoracic level.
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Male or female subjects must be at least 18 years of age.
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Must have a worst pain score ≥6 on the NPRS at Screening visit.
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Subjects not seeking or receiving potentially curative therapies for cancer. Palliative therapy is acceptable if the therapy started and is stable prior to IP administration.
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Sexually active female subjects of childbearing potential and male subjects capable of fathering a child must be willing to use an effective method of contraception to avoid pregnancies.
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Must be willing and capable of understanding and cooperating with the requirements of the study.
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Must be able to understand and complete study-related forms and adequately communicate with the investigator and/or site staff.
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Must have provided written informed consent prior to participating in any study-related activity.
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Subjects able to complete the study duration.
Exclusion Criteria:
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Subjects with leptomeningeal metastases in lumbar area.
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Undergoing or have plans to undergo changes to current cancer treatment during the study through the Day15 assessment.
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Had prior lumbar spine surgical procedures that could impair the ability to perform the injection.
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Evidence of brain pathology or increase intracranial pressure.
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Presence of an IT shunt.
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Has evidence or a coagulopathy or hemostasis problem.
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Subjects with a total neutrophil count <1500 cells/mm3.
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Subjects with serum creatinine ≥1.5 mg/dL.
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Is febrile or has other evidence of an infection within 7 days of planned injection.
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Has an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic contrast agents.
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Female subjects who are pregnant, are planning on becoming pregnant, or are currently breastfeeding.
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Subjects with any medical condition that could adversely impact study participation or assessments.
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Subjects who have received new anti-cancer treatments 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 administration; or had a change in the dose or schedule of the anti-cancer 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 anti-cancer therapy or investigational product prior to completion of the Day 15 visit.
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Subjects with additional loci of pain above the mid-thoracic level or other pain disorder due to non-cancer etiology, unless both the investigator and the subject are clearly able to distinguish the additional pain from the target pain due to cancer.
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Liver cirrhosis or severe hepatic impairment, with liver function test 3 times above ULN.
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Sensory/peripheral neuropathy of CTCAE Grade 2 or higher.
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Nonstudy related minor surgical procedure ≤5 days or major surgical procedure ≤21 days prior to Screening visit.
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Subjects who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies that are CTCAE Grade 3 or higher.
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Arterial thrombi (including stroke), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within 3 months prior to Screening visit.
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Corrected QT using Fridericia's formula (QTcF) prolongation.
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Evidence or history of bleeding disorder within 4 weeks prior to IP administration.
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Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Miami/Sylvester Comprehensive Cancer Center | Miami | Florida | United States | 33136 |
| 2 | Brigham & Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 3 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 4 | Hermann Drive Surgical Hospital | Houston | Texas | United States | 77004 |
Sponsors and Collaborators
- Sorrento Therapeutics, Inc.
Investigators
- Study Director: Monica Luchi, MD, Sorrento Therapeutics, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RTX-001