Page 161 - Fluorescence-guided cancer surgery

Clinical translation of OTL38 in ovarian cancer 159
objectives were to assess the tolerability and pharmacokinetics of OTL38, the e cacy with respect to intraoperative detection of ovarian cancer lesions, and the practical feasibility of the technique. The results were used to determine the optimal dose for intraoperative imaging. Because both studies were exploratory in nature, sample size was not based on a formal calculation of statistical power. In the rst study, tolerability and pharmacokinetics of a single intravenous dose of OTL38 were used as the endpoints. These same endpoints were used in the patient study; in addition, we also measured the e cacy of OTL38 in the intraoperative detection of ovarian cancer by measuring the following endpoints: TBR (tumor-to-background ratio), de ned as the ratio between the uorescent signal in the tumor tissue and the uorescent signal in the tissue surrounding the tumor; concordance between the pathology results with respect to the presence of cancer and the imaging assessment; the number and location of FRα-positive, cancerous lesions identi ed the usual visual and/or tactile approaches with or without uorescence imaging; and the surgeons’ evaluation of the practical application of the technique. Data of all subjects participating in the studies was included in the analyses if the data could meaningfully contribute to the objectives of the studies.
For the study in healthy volunteers, we included 30 subjects who were 18- 65 years of age and were considered healthy based on medical screening. For the patient study, we included twelve patients who had a high suspicion of epithelial ovarian cancer or a tissue-based diagnosis of epithelial ovarian cancer and were scheduled for primary or interval cytoreductive surgery. The main exclusion criteria were current pregnancy, history of anaphylactic reactions, impaired renal function (de ned as eGFR <50 ml/min/1.73 m2), and impaired liver function (de ned as ALT, AST, or total bilirubin levels that exceeded 3X the established upper limit of normal).
The study in healthy volunteers was a randomized, placebo-controlled design in which subjects were randomized to receive a single intravenous dose of 0.025, 0.05, 0.1, or 0.2 mg/kg OTL38 or placebo. The randomization code was generated by a study-independent statistician using SAS 9.1.3 for Windows (SAS Institute Inc., Cary, NC). The randomization code was made available for data analysis only after the study was completed. At xed time points following administration, blood samples were collected and used to measure pharmacokinetics and to perform routine laboratory tests. Adverse events, ECG, and vital signs were recorded. The uorescent signal in super cial skin