A Phase 1 Study of Substance P-Saporin with Histologically Confirmed Advanced Cancer Patients with Chronic Pain
- UT Southwestern Ambulatory Services
Prior to Therapy (28 days before registration)
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.
Day Prior to Treatment: Patients will come to the clinic so the coordinator can collect VaS [Quote]pain bothersomeness[Quote], VaS [Quote]pain intensity[Quote], oDi, SF-36, eQ-5D, BDi, medication use log and the nausea/vomiting diary.
Patients will be treated as an inpatient 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 in the lumbar spine 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. Vital signs will be recorded within 15 minutes following injection. Four hours after injection (+/-15 min), the catheter will be removed and the exit site treated with neosporin ointment and sterilely dressed. after the catheter is removed, the following assessments are made (within 30 minutes after removal): vital signs, physical exam including motor and sensory functions, and electrocardiogram. a neurologist will be available for consultation as needed.
Subjects will be monitored in the recovery room for 4 hours (+/- 30 minutes) then admitted in the hospital for 24 hours to be observed for a total of 24 hours (+/- 2 hours) from injection. Patients only receive a single iT dose.
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
* CBC including differential and platelets
* Serum chemistries
* Serum electrolytes
* 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
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.
1. Age >= 18 years
2. Signed informed consent
3. Cancer patients with pain that is not curable from the umbilicus and below which includes the pelvis, lower abdomen, lower back, legs and feet and who have failed opioid at reasonable doses.
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
11. Patients who are receiving chemotherapy and radiation therapy
12 Patients who may have had received SP-SAP on the study