Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain

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

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.

Study Overview

• Status: Completed
• Conditions: Intractable Cancer Pain
• Intervention / Treatment: Drug: Resiniferatoxin

Detailed Description

All subjects who received RTX will be included in the analyses and summaries of safety, efficacy, PD, and PK assessments.

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami/Sylvester Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham & Women's Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • Houston, Texas, United States, 77004
      • Hermann Drive Surgical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.
• Male or female subjects must be at least 18 years of age.
• Must have a worst pain score ≥6 on the NPRS at Screening visit.
• 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.
• 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.
• Must be willing and capable of understanding and cooperating with the requirements of the study.
• Must be able to understand and complete study-related forms and adequately communicate with the investigator and/or site staff.
• Must have provided written informed consent prior to participating in any study-related activity.
• Subjects able to complete the study duration.

Exclusion Criteria:

• Subjects with leptomeningeal metastases in lumbar area.
• Undergoing or have plans to undergo changes to current cancer treatment during the study through the Day15 assessment.
• Had prior lumbar spine surgical procedures that could impair the ability to perform the injection.
• Evidence of brain pathology or increase intracranial pressure.
• Presence of an IT shunt.
• Has evidence or a coagulopathy or hemostasis problem.
• Subjects with a total neutrophil count <1500 cells/mm3.
• Subjects with serum creatinine ≥1.5 mg/dL.
• Is febrile or has other evidence of an infection within 7 days of planned injection.
• Has an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic contrast agents.
• Female subjects who are pregnant, are planning on becoming pregnant, or are currently breastfeeding.
• Subjects with any medical condition that could adversely impact study participation or assessments.
• 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.
• 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.
• Liver cirrhosis or severe hepatic impairment, with liver function test 3 times above ULN.
• Sensory/peripheral neuropathy of CTCAE Grade 2 or higher.
• Nonstudy related minor surgical procedure ≤5 days or major surgical procedure ≤21 days prior to Screening visit.
• Subjects who have not completely recovered from any toxicities from previous chemotherapy, hormone therapy, immunotherapy, or radiotherapies that are CTCAE Grade 3 or higher.
• Arterial thrombi (including stroke), myocardial infarction, admission for unstable angina, cardiac angioplasty, or stenting within 3 months prior to Screening visit.
• Corrected QT using Fridericia's formula (QTcF) prolongation.
• Evidence or history of bleeding disorder within 4 weeks prior to IP administration.
• Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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: RTX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Grade 3 or 4 Toxicity associated with RTX administration	3-month
Maximum tolerated dose (MTD)	Maximum dose without a Grade 3 or 4 toxicity	3-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Pain Rating Scale (NPRS)	Daily average pain and daily worst pain on a 0-10 scale	Day-28 to Day90 daily

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily analgesic consumption (DAC) log	Consumption of analgesics compared to baseline	Day-28 to Day90 daily
Brief Pain Inventory-Short Form (BPI-SF)	Quality of life compared to baseline by the total score	Day-28, Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90
Patient Global Impression of Change (PGIC)	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.	Day2/3, Day8, Day15, Day30, Day60 and Day90
Modified Numeric Pain Rating Scale (modified NPRS)	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.	Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90
Modified Brief Pain Inventory-Short Form (modified BPI-SF)	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".	Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90

Collaborators and Investigators

• Sponsor: Sorrento Therapeutics, Inc.
• Investigators: Study Director: Monica Luchi, MD, Sorrento Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Actual): March 18, 2020
• Study Completion (Actual): June 18, 2020

Study Registration Dates

• First Submitted: July 6, 2017
• First Submitted That Met QC Criteria: July 20, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): October 20, 2020
• Last Update Submitted That Met QC Criteria: October 19, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Cancer pain; RTX; Resiniferatoxin
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Cancer Pain
• Other Study ID Numbers: RTX-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No