Page 162 - Fluorescence-guided cancer surgery

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Chapter 10
was measured using the Artemis imaging system at xed time points following intravenous administration of OTL38 or placebo (Figure 1). After a dose cohort was completed, all data collected up to 24 hours following each dose were reviewed prior to increasing the dose. In the event of an unacceptable tolerability pro le (based on the nature, frequency, and intensity of adverse events, as judged by the investigator), the dose was not increased. Subjects were assigned to a dosing group based on the order in which they enrolled in the study. The study was performed in a double-blind fashion; thus, the investigator, sta , subjects, sponsor, and monitor were blinded with respect to the treatment until the end of the study. The placebo and OTL38 were formulated and packaged identically. The randomization list was made available only to the pharmacist who prepared the study drug, the individual who was responsible for sample bioanalysis, and the statisticians and programmers who prepared the blinded summaries, graphs, and listings to support the dosing decisions.
The patient study was a single ascending dose, open label exploratory study. The patient study was not randomized, and all patients received the active drug. Assignment to the dosage groups was based on the order in which the patients enrolled in the study. The patients received a one-hour intravenous infusion of OTL38 2-3 hours prior to the start of surgery. A dose-escalating scheme with planned doses of 0.025, 0.05, and 0.1 mg/kg (and the possibility to decrease the dose to 0.0125 mg/kg) was used. Dose escalation was terminated in the event of an unacceptable tolerability pro le. Tolerability assessment (blood pressure, pulse, peripheral oxygen saturation, respiratory rate, ECG, temperature, and skin assessments) and blood collection for pharmacokinetics and routine laboratory tests were performed at regular intervals starting just prior to administration and lasting until 24 hours post-dosing. Adverse events and the concomitant use of other medications were recorded. Cytoreductive surgery generally included the removal of the uterine adnexa, uterus, and infracolic omentum, as well as resection of all macroscopic tumors, where possible. All surgical procedures were open procedures performed by an experienced gynecological oncologist using a midline abdominal incision. First, the primary tumor and metastases were identi ed in the surgical eld using standard visual and tactile methods. Thereafter, the Artemis imaging system was used to identify NIR- uorescent lesions. All tumor tissue identi ed by visual/tactile methods and/NIR uorescence was resected, provided it was both surgically feasible and clinically useful. Each resected lesion was marked on a case report