A Phase 1 Study of Substance P-Saporin in Terminal Cancer Patients with Intractable Pain

Study ID
STU 102013-010

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • UT Southwestern Ambulatory Services
  • UT Southwestern University Hospital—St. Paul
  • UT Southwestern University Hospital– Zale Lipshy

Contact
Joyce Bolluyt
214-648-7007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Arthur Frankel

Summary

Prior to Therapy (-7 days to Day 0)
informed consent will be obtained. Following consent, a history, exam, blood sample for pretreatment antibody response, and screening tests will be completed to confirm eligibility, including pregnancy testing for females of childbearing potential. Physical examination of sensory and motor function will be performed once during an office visit during this period. For each day of the week before treatment, the following pain level parameters will be recorded and documented daily by the subject in the provided diary: VaS [Quote]pain bothersomeness,[Quote] VaS [Quote]pain intensity,[Quote] oDi, SF-36, eQ-5D, BDi and medication use log. in addition, the frequency of nausea and emesis will be documented daily in the subject's diary. information from the diary will be collected for analysis on a weekly basis.

Therapy
Patients will be treated on an outpatient basis. on the day of treatment, subjects will arrive at the university of Texas Southwestern Medical Center two hours prior to treatment to allow for collection of vital signs, subject diary information, safety and efficacy assessments, and eligibility assessments. The first subject will be enrolled in the 1-mcg SP-SaP cohort. a percutaneous intraspinal catheter will be placed at the L5-S1 interspace and the catheter advanced 4-5 cm into the intrathecal space under fluoroscopic guidance. To confirm location, CSF will be aspirated and radioopaque contrast dye injected. 1-mL study drug will be mixed with 1-mL patient CSF fluid and administered intrathecally via the catheter. The catheter will be flushed with 1 mL bolus of saline. Four hours after injection (+15 min), the catheter will be removed and the exit site treated with neosporin ointment and sterilely dressed. Subjects will be monitored in the recovery room for 4 hours and in the hospital for 24 hours and discharged home. Patients only receive a single iT dose. Vital signs will be recorded immediately following injection. after the catheter is removed, the following assessments are made: vital signs, physical exam including motor and sensory functions, and electrocardiogram. a neurologist will be available for consultation as needed.

Post Therapy
Subjects will return for weekly office visits for the first eight weeks and then monthly for four months. During the office visits, the following evaluations will be performed:
* Vital signs
* Sensory/motor exam as part of physical examination
* Blood samples for immune response measurements
* electrocardiograms
* CBC including differential and platelets
* Serum chemistries
* Serum electrolytes
* urinalysis
* Pain level quantification using: VaS [Quote]pain intensity[Quote] and [Quote]pain bothersomeness,[Quote] oDi, SF-36, eQ-5D, BDi, medication use log and nausea/emesis diary

endpoints:
1. Dose limited toxicity.
2. Toxicity profile.
3. Maximal tolerated dose
4. Clinical respone rate.
5. Substance P and Saporin antibodies in serum pretreatment and weekly for eight weeks.

Participant Eligibility

1. Age >= 18 years
2. Signed informed consent
3. Terminally ill cancer patients with intractable chronic pain in the pelvis, lower abdomen, back, or spine.
* Terminal
* refers to <= six-month life expectancy.
* Intractable
* is defined as pain uncontrolled with medications or procedures.
4. Minimal expected survival time of one month
5. ECOG Performance status of 0 - 3
6. Able to verbally report pain
7. Able to indicate pain on a VAS
8. Able to perform motor/sensory tests
9. Able to undergo a 4-h intrathecal catheter placement
10. Other therapeutic and palliative options have been exhausted