Abstract CT030: Preliminary results from a phase I study of Substance P-Saporin in advanced cancer patients with intractable pain
Authors: Frankel Arthur E. , Lappi Douglas A. , Noe Carl , Higgins Denise , Russell Brian J. 
Published: July 2016

Abstract
Cancer pain is a great fear, at times greater than even death, in the progression of the disease. 10-15% of cancer patients have pain that is refractory to opioid treatment. There is a common fear among terminal patients that pain treatments will leave them unable to function normally at a time when that is extremely important for them. Substance P-Saporin (SP-SAP), targets with Substance P (SP), a neuromodulator that binds to receptors on laminae I and X of the dorsal horn of NK1r-bearing neurons. These neurons are critical components of the high level, intense pain pathway. The toxic portion of the drug is Saporin (SAP), a ribosome-inactivating protein that, once assisted inside a cell by Substance P, ablates neurons that express NK1r. A single intrathecal infusion of SP-SAP alleviated pathologic pain perception without affecting other sensory signal pathways in preclinical studies conducted in rats. Studies published in the journal Science show pathological pain relief is permanent with no long-term side effects such as central sensitization. A veterinary single-blind clinical trial for the treatment of pain associated with bone tumors in canine companion animals showed that after one injection of SP-SAP, dogs had a much higher quality of life throughout the cancer.
Patients in the ongoing SP-SAP phase I clinical trial (NCT02036281) are treated at University of Texas Southwestern. Eligibility: 18 years or older, signed consent, able to verbally report pain, able to complete pain surveys, perform motor/sensory tests, able to undergo intrathecal catheter placement, other therapeutics and palliative options have been exhausted, and have been diagnosed with advanced cancer leading to intractable pain with minimum expected survival of one month. Treatment: a percutaneous intraspinal catheter is placed at the L5-S1 interspace and the advanced 4-5 cm into the intrathecal space under fluoroscopic guidance. 1 mL SP-SAP is mixed with 1 mL patient CSF fluid and administered via the catheter. Subjects are monitored for four hours in the recovery room before catheter is removed, monitored in hospital 24 hours, and discharged. The starting dose of SP-SAP was 1 mcg in 1mL, 1/10th the dog no observable adverse effect level. Dose: Single subject cohorts are at doses of 1, 2, 4, 8, 16, 32, 64, and 90 mcg. If a drug-related dose-limiting toxicity is observed in two or more patients in a cohort, the maximal tolerated dose (MTD) has been exceeded, and the next lower dose level will be the MTD. An additional 15 patients will be treated at the MTD to confirm safety. Endpoints: Response measurements include pain level measurements, Brief Pain Inventory (BPI), VAS “pain bothersomeness,” VAS “pain intensity,” ODI, SF-36, EQ-5D, BDI, and Medication Use logs in patient diary. Primary endpoints for the trial are either a 20% reduction in pain scores or a 20% reduction in pain medications taken by the patient.
Citation Format: Arthur E. Frankel, Douglas A. Lappi, Carl Noe, Denise Higgins, Brian J. Russell. Preliminary results from a phase I study of Substance P-Saporin in advanced cancer patients with intractable pain. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT030.