Study of SS1(dsFv)-PE38 (SS1P) Anti-Mesothelin Immunotoxin in Advanced Malignancies: Continuous Infusion for 10 Days
Although Neopharm has terminated its sponsorship of this study, it is continuing under the sponsorship of the NCI. Please see "Experimental Drug SS1(dsFv)-PE38 to Treat Cancer" (Study ID number 010011).
SS1(dsFv)-PE38 is an oncology drug product containing a bacteria toxin, fused to a high affinity, disulfide stabilized antibody. The fused protein retains cell killing activity, but binds only to cells expressing mesothelin. Tumors characterized by very high surface mesothelin expression include mesothelioma; epithelial carcinomas of ovary and peritoneum; and squamous cancers of cervix and upper aerodigestive tract, including esophagus, head, and neck cancers.
This is a dose-escalating study to determine the maximum tolerated dose (MTD) of intravenous SS1(dsFv)-PE38 administered continuously for 10 days every four weeks for a maximum of four courses of treatment. Dose escalation will proceed in cohorts of 3 until dose-limiting toxicity (DLT) is observed.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Study Start Date:||February 2001|
OBJECTIVES: I. Investigate the safety and efficacy of SS1(dsFv)-PE38 administered as a 10-day continuous intravenous infusion.
II. Determine the toxicities and maximum tolerated dose (MTD) of SS1(dsFv)-PE38 given by continuous intravenous infusion for ten days in patients with advanced malignancies.
III. Evaluate response of selected advanced malignancies to continuous intravenous infusion of SS1(dsFv)-PE38 for ten days at doses near the MTD.
IV. Characterize the plasma kinetics of SS1(dsFv)-PE38 administered by continuous intravenous infusion.
V. Determine the appearance of serum antibody to SS1(dsFv)-PE38.
PROTOCOL OUTLINE: To exclude immediate allergic hypersensitivity reaction, each patient will receive a test dose of SS1(dsFv)-PE38, and be observed for 30 minutes prior to receiving the continuous infusion on Day 1 of each treatment course. Each treatment will be given by continuous intravenous infusion for ten days. After the first 24 hours of infusion, at the Investigator's discretion, patients will be allowed to leave the hospital on day pass per NCI policies. After the end of infusion patients will be observed overnight. The first patient at each dose level must be observed for development of toxicity for at least 14 days after the beginning of treatment before additional patients are enrolled. At least three patients will be accrued at each dose level. Dose escalation within a patient will not be allowed.
PROJECTED ACCRUAL: Up to 30 patients