Clinical trial NCT03226574: Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Intractable Cancer Pain
Keywords: Resiniferatoxin
RTX
Cancer pain
Lead sponsor: Sorrento Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2017-07-24
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: The design uses a traditional "3+3" rule-based design that does not stipulate any prior assumption of the dose-toxicity curve. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.
Primary purpose: TREATMENT

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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: 3-month
measure: Maximum tolerated dose (MTD)
timeFrame: 3-month
Secondary outcomes:
measure: Numeric Pain Rating Scale (NPRS)
timeFrame: Day-28 to Day90 daily
Other outcomes:
measure: Daily analgesic consumption (DAC) log
timeFrame: Day-28 to Day90 daily
measure: Brief Pain Inventory-Short Form (BPI-SF)
timeFrame: Day-28, Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90
measure: Patient Global Impression of Change (PGIC)
timeFrame: Day2/3, Day8, Day15, Day30, Day60 and Day90
measure: Modified Numeric Pain Rating Scale (modified NPRS)
timeFrame: Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90
measure: Modified Brief Pain Inventory-Short Form (modified BPI-SF)
timeFrame: Day1, Day2/3, Day8, Day15, Day30, Day60 and Day90
Locations:
city: Miami
country: United States
facility: University of Miami/Sylvester Comprehensive Cancer Center
state: Florida
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: Hermann Drive Surgical Hospital
state: Texas
Study officials:
affiliation: Sorrento Therapeutics, Inc.
name: Monica Luchi, MD
role: STUDY_DIRECTOR
References: