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

Screening (-7 days to Day 0)

• Physical exam and medical history;
• Vital signs;
• Blood tests;
• Pain measurements (6 daily pain questionnaires for 7 days prior to receiving study drug);
• Urine tests;
• Pregnancy test;
• Electrocardiogram (EKG), a tracing of the electrical activity of the heart;
• Collection of demographic information (age, sex, ethnic origin);

Study Drug:

SP-SAP will be administered via a spinal injection. Depending on when the subject is enrolled in the study, the dose of SP-SAP will be between 1 and 90 micrograms of SP-SAP

Therapy:

Subject will arrive at the UTSW Eugene McDermott Center for Pain Management 2 hours prior to treatment. The following will take place:

• Physical exam;
• Pain measurements (6 pain questionnaires);
• EKG;
• The subject will have a catheter inserted into their spine and will receive the study drug intrathecally (into their spine). The catheter will remain in their spine for 4 hours. Less than 1 tablespoon of spinal fluid will be collected for research purposes; and
• They will remain in the University of Texas Southwestern Medical Center Hospital for 24 hours for observation as a precaution.

Follow-Up will occur weekly for 8 weeks and then monthly for 4 months as needed.

During these visits the following will take place:

• Physical exam (including sensory and motor skills) and medical history;
• Vital signs;
• Two tablespoons of blood will be drawn from your arm by needle stick for blood tests;
• Pain measurements (6 pain questionnaires);
• Urine tests; and
• Electrocardiogram (EKG), a tracing of the electrical activity of the heart.

The subject will be asked to keep a diary to record any nausea and vomiting as well as a medication log to record the pain medications and dosage that they take between visits.

Each visit will take approximately 2 hours to complete

4 Month Follow-Up Informational data on the level of pain, adverse events, and sensory and motor function will be collected for the remaining 4 months of the study or until time of death. This information may be collected via patient diary, office visit or telephone interview.

Inclusion criteria

• Age ≥ 18 years
• Signed informed consent
• 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.
• Minimal expected survival time of one month
• ECOG Performance status of 0 - 3
• Able to verbally report pain
• Able to indicate pain on a VAS
• Able to perform motor/sensory tests
• Able to undergo a 4-h intrathecal catheter placement
• Other therapeutic and palliative options have been exhausted

Exclusion criteria

• Concurrent therapy with an investigational agent
• Concurrent radiation or chemotherapy
• Pregnancy or failure to use effective contraception in fertile males or females, and breast-feeding females. For all female patients of child-bearing potential, a negative pregnancy test (serum or urine) within ten days before start of the study treatment must be obtained. Female patients must agree to use effective contraception, or must be surgically sterile, or must be postmenopausal. Acceptable forms of birth control are: spermicide with condom, diaphragm, or cervical cap, IUD-intrauterine device, birth control pills, or abstinence. The rhythm method or Plan B are not considered acceptable forms of birth control. Male patients must agree to use effective contraception or be surgically sterile.
• Diagnosis of intractable chronic pain of the chest, head, neck or upper extremities.
• Active infection or ulcer at the lumbar injection site
• Inability to receive lumbar intrathecal injection because of other factors
• Diagnosis of meningitis or encephalitis
• Other severe, acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or, in the judgment of the investigator, would make the patient inappropriate for the study
• Comorbidities at particular risk (i.e., CNS, CNS metastases, hydrocephalus or coagulopathy)